Next Article in Journal
HCIV-1 and Other Tailless Icosahedral Internal Membrane-Containing Viruses of the Family Sphaerolipoviridae
Next Article in Special Issue
Bat Astroviruses: Towards Understanding the Transmission Dynamics of a Neglected Virus Family
Previous Article in Journal
Genetic Assessment of African Swine Fever Isolates Involved in Outbreaks in the Democratic Republic of Congo between 2005 and 2012 Reveals Co-Circulation of p72 Genotypes I, IX and XIV, Including 19 Variants
Previous Article in Special Issue
A Review of the Strain Diversity and Pathogenesis of Chicken Astrovirus
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Viruses
Volume 9
Issue 2
10.3390/v9020033
viruses-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Epidemiology of Classic and Novel Human Astrovirus: Gastroenteritis and Beyond

by
Diem-Lan Vu
1,2,
Albert Bosch
1,2,
Rosa M. Pintó
1,2 and
Susana Guix
1,2,*
1
Enteric Virus Laboratory, Department of Genetics, Microbiology and Statistics, University of Barcelona, Barcelona 08028, Spain
2
Nutrition and Food Safety Research Institute (INSA-UB), University of Barcelona, Santa Coloma de Gramenet 08921, Spain
*
Author to whom correspondence should be addressed.
Viruses 2017, 9(2), 33; https://doi.org/10.3390/v9020033
Submission received: 29 November 2016 / Revised: 12 February 2017 / Accepted: 13 February 2017 / Published: 18 February 2017
(This article belongs to the Special Issue Astroviruses)
Browse Figure
Versions Notes

Abstract

:
Since they were identified in 1975, human astroviruses have been considered one of the most important agents of viral acute gastroenteritis in children. However, highly divergent astroviruses infecting humans have been recently discovered and associated with extra-intestinal infections. The report of cases of fatal meningitis and encephalitis, especially in immunocompromised individuals, has broadened their disease spectrum. Although zoonotic transmission among animal and human astroviruses has not been clearly recognized, the genetic similarity between some human and animal viruses makes it likely to occur. This review provides an update on the epidemiology of both classic and novel human astroviruses, and a comprehensive view on confirmed or potential association between astrovirus and human disease.

1. Introduction

Since their first discovery in 1975 in the stool samples of children with diarrhea [1], human astroviruses (HAstVs) have been well-established etiological agents of viral gastroenteritis with a worldwide distribution [2,3]. They are small, non-enveloped, single-stranded positive RNA viruses and they make up the Astroviridae family. To date, the family has been divided into two genera: Mamastrovirus and Avastrovirus, including viruses infecting mammals and birds, respectively. Their genome codes for three open reading frames (ORFs), with ORF1a and ORF1b encoding the nonstructural protease and polymerase proteins, respectively, and ORF2 encoding the capsid proteins. While they have been reported in cases of adult gastroenteritis, they are predominantly considered a common cause of viral gastroenteritis in the pediatric population, after rotavirus and norovirus. In addition to children, HAstV gastroenteritis also frequently occurs in the elderly [4] and in immunocompromised individuals [5,6,7,8].
Since 2008, two novel groups of highly divergent astroviruses, named MLB (Melbourne) and VA/HMO (Virginia/Human-Mink-Ovine-like), have been identified in human stool of individuals with diarrhea using next-generation sequencing (NGS) [9,10,11,12,13,14]. Although these new viruses were initially isolated in children with gastroenteritis, the number of systematic epidemiological studies to determine their true prevalence is still low, and no definitive association between novel astroviruses and gastroenteritis has yet been established. In addition, both classic, but especially novel, HAstVs have recently been identified as the cause of unexpected central nervous system (CNS) infections in vulnerable individuals, highlighting that these viruses may bypass the gastrointestinal tract and infect other tissues and organs [15].
The aim of this review is to describe the recent findings on both classic and novel HAstV in terms of viral diversity, tropism, disease association, and prevalence, and identify potential knowledge gaps for future investigations.

2. Classification

The level of amino acid identity between MLB-AstVs, VA/HMO-AstVs, and classic HAstVs is very low (Table 1), suggesting that there may be significant biological and antigenic differences between them. On average, identities between MLB and classic HAstVs are 33%, 54%, and 27% for ORF1a, ORF1b, and ORF2, respectively. For VA, the average identities with classic HAstVs are slightly lower (24%, 52%, and 24% for each ORF, respectively).
Classical HAstVs are classified into eight serotypes (HAstV-1 to HAstV-8) with 64%–84% capsid amino acid similarities between them. According to the International Committee on Taxonomy of Viruses (ICTV), this group defines Mamastrovirus 1 species within the Mamastrovirus genus (Table 1). Although serotype-specific neutralizing antibodies may be detected in sera from infected individuals, suggesting a lack of heterotypic immunity, further studies are required to assess whether cross-protection may occur between serotypes. Within each serotype, different genetic lineages or subtypes can also be identified, based on a lower than 93%–95% nucleotide homology of partial ORF2. Lineage classification has been recently reviewed in [2,16], with six lineages within HAstV-1 (1a to 1f), four within HAstV-2 (2a to 2d), two within HAstV-3 (3a and 3b), three within HAstV-4 (4a to 4c), three within HAstV-5 (5a to 5c), and two within HAstV-6 (6a and 6b). The subsequently-identified HAstV-3c should be added to the classification [17]. Whether there is a significant biological difference between lineages is still poorly understood; although not fully addressed yet, some of them may share some ORF1a1b genes and recombination may significantly contribute to enhanced diversification and evolution. A classification system based on both ORF1b and ORF2, similar to what has been established for similar viruses, such as noroviruses [18], would be extremely informative.
Compared to classic HAstVs, novel HAstVs are even more diverse. MLB-HAstVs (Mamastrovirus 6) is classified in three types or clades (MLB1, MLB2, and MLB3), while VA HAstVs are divided in Mamastrovirus 8 species, containing VA2 (also named HMO-B) and VA4, and Mamastrovirus 9 species containing VA1 (also named HMO-C) and VA3 (HMO-A) [2,15,19]. Although not yet officially recognized by the ICTV, and based on the capsid homology, the recently identified VA5 clade [20,21] may be classified as a new species. Since no specific antisera against novel HAstVs are available, the correlation between these clades and serotypes has not yet been experimentally confirmed.

3. Diversity and Zoonotic Potential

Astrovirus demonstrate a high genetic diversity leading to the potential infection of a large spectrum of mammals and birds [22]. Figure 1 provides an exhaustive view of astrovirus host species and reveals that the distance between distinct virus species infecting humans is higher than the distance between HAstVs and some of those infecting animal species. Bats and pigs harbor the highest astrovirus strain diversity, suggesting their role as potential reservoirs. Astrovirus infecting bats are not known to infect other species, but a recombinant virus between pig and HAstVs have been described, suggesting that they may have crossed the species barrier [23]. Emerging diagnostic tools, such as NGS, continue to discover additional astrovirus host species [24,25,26]. It remains unknown if these findings reflect astrovirus genetic evolution, or if these viruses were formerly unrecognized because they were not targeted by the detection assays.
The high genetic variability of HAstVs, together with the occurrence of recombination events during concurrent infections with multiple strains, makes them serious candidates for emerging zoonotic infections. Cross-species transmissions are especially frequent in avian viruses [28]. A recent investigation on non-human primates shows that they can be infected by different astrovirus strains closely related to those usually infecting either other mammals, avian species, or even humans, including the novel HAstV MLB [29]. In humans, antibodies directed toward non-human astroviruses have been identified [30]. Thus, there is certainly an overlap between animal and human astrovirus strains, and there are more and more data suggesting that astrovirus infections are not species specific. Interestingly, a novel astrovirus-like virus has recently been detected in stools of individuals infected with the human immunodeficiency virus (HIV) and healthy individuals [31]. This new virus, tentatively named Bastrovirus, shows the closest homology to HAstV MLB at the capsid level, and to members of the Hepeviridae family at the nonstructural proteins level, pointing to a putative recombination event between members of these two close viral families.

4. Pathogenesis and Disease Spectrum

4.1. Astrovirus in the Gastrointestinal Tract

Classic HAstVs are a frequent cause of mild gastroenteritis in children under two to five years of age, usually causing a self-limiting disease, notably two- to three-day watery diarrhea. Human and turkey astrovirus capsid protein have been shown to act like an enterotoxin and induce intestinal epithelial barrier dysfunction, according to in vitro and animal models, respectively [32,33]. Vomiting is less prevalent in astrovirus infection than in rotavirus or norovirus infection, and the incubation period is a little bit longer. In neonates, an association between HAstV infection and necrotizing enterocolitis has been observed by two independent studies [34,35].
The causal link between novel HAstVs and acute gastroenteritis has been studied in case-control studies, with inconsistent results. While Holtz et al. did not find any association between MLB1 and diarrhea in a cohort of Indian children [36], Meyers et al. reported an association for MLB1, but not for MLB2, VA1, and VA2 in Kenya and Gambia, and even a higher prevalence of MLB3 in control subjects [20]. While Holtz et al. did not observe differences in viral load between cases and controls, the reported titers (7 × 103 and 4 × 104 RNA copies/mL of fecal suspension) were strikingly lower than those usually found in classic HAstVs infections. Whether HAstV MLB1 replicates to a lesser extent than classic HAstVs, and if this contributes to the lack of association with diarrhea, if any, remain to be clarified.
In addition, the fact that astrovirus can be recovered in feces of asymptomatic children [20,37,38,39] and mammals [40] raises the question of whether it simply reflects astrovirus prolonged shedding or nucleic acid persistence, or if astrovirus virions can persist in some way in the gastrointestinal tract, and be part of the gut virome. If so, the determinants of such a persistent infection need to be explored, as well as those that can trigger an increase in viral replication or a recurrent pathogenic infection, as this can potentially lead to severe local or disseminated infection [41]. Further studies confirming the qualitative or quantitative role of novel HAstVs in gastroenteritis are imperative.
Finally, the role of astrovirus as part of the gut virome, interacting with other component of the gut microbiome and the immune system should also be taken into account for further studies. In the poult enteritic syndrome [42], turkeys demonstrate growth retardation and behavioral changes that potentially derive from digestive disorders, but could also be linked to the gut-brain axis [43]. Yet, astrovirus is frequently identified in co-infection with other enteric pathogens [20,44], with potentially complex pathogenesis involving transkingdom interactions [45], as suggested by Qureshi et al. in their study demonstrating a reduced uptake of Escherichia coli by macrophages in presence of turkey astrovirus [46].

4.2. Astrovirus beyond the Gastrointestinal Tract and in Other Organs

Beside the gastroenteritis classically seen in children and the elderly, HAstVs have recently been associated with encephalitis and meningitis in immunocompromised patients (reviewed in Reference [15]); this is particularly true for the VA1/HMO-C genotype, which has been identified in five cases of encephalitis so far [47,48,49,50,51], but also for the MLB group [52,53] and the classic HAstVs [41]. Table 2 summarizes these nine cases of CNS infection in humans. Only one case affected an immunocompetent adult woman, who recovered from a MLB2 self-limited CNS infection. Among the remaining cases, six of them were fatal. Close contact with animals and young children, intravenous immunoglobulin treatment and the stem cell graft have all been suggested as possible source of infection, but none has been confirmed. Viral load in brain biopsy specimen can be as high as 1.5 × 107 RNA molecules per reaction [47], sometimes 103-fold higher than in cerebrospinal fluid (CSF) and 106-fold higher than in stool [48]. These results point out that analysis of superficial samples, such as CSF or stools, can be insufficient and that analysis of profound specimens (brain biopsies) may be required in order to make a diagnosis.
In animals, astrovirus has also been associated with CNS infection, causing suppurative encephalitis in several bovid [54], the shaking-mink syndrome [55], and potentially being associated with congenital tremor syndrome in piglets [56]. Thus, astrovirus’ tropism for the CNS appears to be highly plausible. Like enteroviruses, HAstVs may cause a wide disease spectrum, depending on specific virus and host factors, which remain to be characterized and which may ultimately determine the outcome of infection.
Virus–host interaction studies disclosing how adaptive and innate immunity control HAstV infection and dissemination beyond the gastrointestinal tract are in progress. Adaptive immunity has been shown to be important both in human and animal studies [57,58,59]. In mice deficient in adaptive immunity, viral replication in the gastrointestinal tract is increased, and viral RNA has also been detected in the mesenteric lymph nodes, spleen, liver, and kidney. No RNA has been identified in extra-digestive organs of wild-type mice [58]. The importance of innate immune responses (type I interferon ) in limiting viral replication has been recently shown by in vitro studies for classic HAstVs [60] and in vivo for avian and mice viruses [61,62].
Finally, NGS analysis has also allowed the identification of MLB2 and VA1 in plasma or nasopharyngeal swabs of children with fever and acute respiratory disease of unknown etiology [63,64,65]. Again, large prospective prevalence investigations are needed to better understand the clinical relevance of these findings.
Given the wider tissue tropism and disease spectrum of animal astroviruses (for a review see References [66,67]) together with their high zoonotic potential, close attention should be paid to the emergence of strains that could cause unexpected diseases in humans.

5. Prevalence and Distribution

5.1. Classic HAstVs

Classic HAstVs are ubiquitous but their burden is noteworthy in developing countries. Prevalence among children with gastroenteritis, in studies using real time PCR (RT-PCR) screening method, is about 5% (ranges from 0 to over 20%) (Table 3). Although HAstV incidence seems to decrease over the last decades, higher positivity rates are still observed in areas such as China or South America [68,69]. Prevalence is higher among outpatients compared to hospitalized children. HAstV is estimated to contribute to nosocomial infections in approximately 5% of cases [70,71]. For unknown reasons, studies using multiplex RT-PCR for screening tend to generate lower prevalence [72,73,74,75].
Although controversial, HAstV infection mostly occurs during winter season. Epidemiological studies have shown a higher burden of HAstV diarrhea every other year. Regarding the incidence of different serotypes, HAstV-1 is by far the most prevalent type worldwide, accounting for over 50% of cases in all recent reports (Table 3), while the second most frequent differs depending on geographical localizations. Geographical and temporal distribution of the different genetic lineages within each serotype, including HAstV-1, has not been systematically addressed: Whether some lineages are constantly prevalent or whether a turnover of lineages occurs over time is unclear. While some HAstV-1 strains have been detected for 10 consecutive years in the same area [101], some other lineages have been shown to emerge or re-emerge over time [102]. Systematic lineages surveillance would help to understand the driving forces of HAstV evolution.
With the drastic increase in sensitivity of real-time RT-PCR method, a significant higher positivity rate of HAstVs among asymptomatic children has been reported [88,90,103], being approximately 4%, but reaching up to over 20% in some studies [38] (Table 3). Accurate viral load quantification will be important to determine whether the degree of viral replication may contribute to explain the clinical outcome of HAstV infection. In this regard, a community-based birth cohort study performed in Tanzania, using TaqMan array cards targeting 19 enteropathogens, showed no association between diarrhea and qualitative results, but found a significant association for astrovirus, rotavirus and Shigella/enteroinvasive E. coli with quantitative results [104]. As already mentioned, co-infections of HAstVs with other enteric viruses are often reported, and there are data indicating a significant correlation between co-infections and clinical disease [90]. Of note, the average rate of HAstV co-infections, especially with enteric viruses, is over 30%, making association with gastroenteritis more challenging.

5.2. Major Reported Outbreaks

Although classic HAstVs are typically involved in sporadic cases of gastroenteritis, and although most viral gastroenteritis outbreaks worldwide are caused by noroviruses [105], noteworthy HAstV outbreaks have also been described worldwide. Yet, HAstV has been implicated in 0.5% of all acute gastroenteritis outbreaks reported from 1994 to 2005 in the Netherlands [106]. A prospective study in the US also shows that HAstVs may cause 10% of all reported outbreaks in day-care centers [107]. Outbreaks classically occur in schools, nursing homes and hospitals [4,106,108,109,110], but can also affect neonatal care units and maternity wards [111,112]. Interestingly, an outbreak among young healthy adults in a riot police camp in Korea was caused by HAstV serotype 5, which is rarely identified in sporadic cases of HAstV gastroenteritis [113].

5.3. Novel Astroviruses

Novel HAstVs have also been identified worldwide, without significant differences between industrialized and developing countries. A recent review on novel astrovirus epidemiology [15] shows an overall positivity rate in stool lower than those observed for classic HAstVs (1.5%) (Table 4). In only one study from Japan, MLB-HAstVs have been found in a higher proportion than classic HAstVs (10.6%) [84]. Unexpectedly, despite this apparent low overall prevalence, serological studies in the US have reported a surprisingly high HAstV-MLB1 and HAstV-VA1 (HMO-C) seroprevalence (86% and 65%, respectively) [114,115]. Thus, the development and optimization of sensitive diagnostic methods and the more systematic screening for novel HAstVs are mandated to provide a valuable estimate of their prevalence.
The publication of several case reports of meningitis and encephalitis caused by novel HAstVs infection has prompted research groups to retrospectively screen largely for novel HAstVs in CSF samples [48,52]. The observed positivity rate is low (0–0.2%), suggesting, that either HAstVs CNS infection is of very rare occurrence, or the targeted population and/or type of specimen are not adequate.

6. Transmission Routes

Classic HAstVs are essentially transmitted through the fecal–oral route, as demonstrated by human volunteer studies [119,120]. HAstV has also been proven stable enough in the environment to undergo vehicular transmission through drinking [121] of fresh or marine water [122]. They can be found in sewage [123,124] and, like other viral pathogens, are not completely removed from sewage after wastewater treatment [125]. Prevost and co-workers reported median viral loads of 2.69 × 103 genome copies/L, similar to other common enteric viruses, such as noroviruses, in wastewater treatment plant effluents in Paris [126]. Novel HAstVs have also been commonly detected in sewage samples, although their prevalence may be lower than classic HAstV [127,128], reflecting either a lower number of infected individuals, a lower viral shedding and/or persistence, or less sensitive detecting methods. In any case, both classic and novel HAstV are ultimately discharged into fresh and marine water environments [129,130,131].
Surface and ground waters are routinely employed as source of drinking water, representing a major public health threat when water quality is poor. According to the World Health Organization (WHO), children in developing area are particularly vulnerable to gastroenteritis attributable to unsafe water, and poor sanitation and hygiene [132]. As such, endemic waterborne astrovirus represents a significant cause of digestive illness as demonstrated by a French surveillance study [133]. Infectious HAstVs have also been detected in tap water in Ghana [134] and in dam water where sewage effluents from an area reporting concurrent gastroenteritis outbreak circulate [131]. A report from Slovenia described HAstVs in 1.4% of drinking groundwater supplies and in 27% of surface water samples [135].
The public health risks associated with bathing and other recreational activities in sewage-polluted waters is much lower than for consumption of contaminated water, but is, nevertheless, not negligible. A study performed in the UK revealed a much higher HAstV seroprevalence in surfers than in the control population [136]. In addition, investigation of an outbreak of gastroenteritis in children and adults bathing in an outdoor pool in Helsinki revealed water contaminated with HAstVs and noroviruses [137].
Infrequently, HAstVs have been implicated in large foodborne gastroenteritis outbreaks. One report describes as many as 4700 individuals infected by contaminated food from a common supplier [109]. Similar to other foodborne viruses, the matrices most often associated with HAstV outbreaks are live bivalve mollusks, grown and harvested in polluted environments, salad greens and soft fruits irrigated with contaminated waters.
Inadequate food handling leads to contamination of ready-to-eat food products that are consumed with little, if any, cooking process. HAstV infections may result in asymptomatic virus shedding in adults too [138,139,140], and asymptomatic food handlers are more frequently the source of foodborne outbreaks than symptomatic ones, whatever the causing virus is [141].
In institutional settings such as hospitals, day-care centers or geriatric centers, fomites play an important role on the vehicular transmission of HAstV [142,143], which may persist dried on inanimate surfaces long enough and at sufficiently high viral load to represent a significant health threat [144] to vulnerable hosts. Classic HAstVs may survive for at least two days at room temperature in non-porous materials, such as toilet tiles, and for at least one week in porous materials, such as toilet paper or bed linen [144].

7. Control and Prevention

Prevention of HAstV infections mostly relies on the control of virus transmission. The best measure to avoid person-to-person transmission is the frequent hand washing with soap and water, especially after using the toilet and changing diapers, and before eating or preparing food. Disinfection of potentially contaminated fomites is also highly recommended. Alcohol (90%) has been proven to be useful for non-porous fomites and hand disinfection [145]. Unfortunately, to date, there are no data on survival and inactivation methods of novel HAstVs, but the use of bleach is recommended.
Astrovirus detection and inactivation in water and food are also the best means to prevent waterborne and foodborne astrovirus outbreaks. Although several methods for the detection and quantification of HAstVs exist, they are not routinely screened in at-risk water and food matrices. Classic HAstV demonstrate a prolonged survival in drinking water and disinfection with 1 mg/mL of free chlorine for two hours is required for successful inactivation [121]. Of note, the environmental persistence differs between strains, Serotypes 6 and 7 (genogroup B based on ORF1a phylogeny), have an increased resistance to chlorine disinfection compared to serotypes 1–5 and 8 (genogroup A based on ORF1a phylogeny) [124].
To prevent disease development, vaccination and potentiation of the natural defenses, such as the gut microbiota, are thought to be the most efficient measures. However, there are no available commercial vaccines for HAstVs. Virus-like particles (VLP) for some classic strains, produced in different recombinant expression systems have been described [146,147], which could be good antigen candidates for an inactivated vaccine. Recently, two subunit vaccine candidates, based on the spike P protein of an avian astrovirus fused together with the spike P protein of hepatitis E virus and the spike P protein of a norovirus or the VP8 protein of rotavirus, have been described to elicit a good IgG response in mice [148,149]; a similar approach could be intended with HAstV. Yet, the lack of commercial interest in HAstV vaccine production may rely on the low clinical impact of the classic HAstV infections in healthy patients and on the need of a multivalent vaccine to cover all circulating serotypes or at least the most prevalent. As for the novel HAstVs, although they may be clinically more relevant, their low prevalence does not draw the attention of the vaccine manufacturing industry.
Treatment for serious gastroenteritis consists of oral or intravenous fluid replacement to avoid dehydration. Immunocompromised hosts with severe or persistent diarrhea may receive intravenous immunoglobulins, although their true efficacy has yet to be established in large-scale studies [150]. To date, there is no known specific treatment for novel astrovirus CNS infection; corticosteroids, ribavirin, and PEG-interferon have been described in case reports [49,50] without a clear efficacy. Consequently, the current measures include supportive treatment and restoration of immunity. The emergence of neuroinvasive astrovirus strains requires investigations for the successful treatment of severe CNS complications.
Water treatments with chlorine and synthetic flavonoids have been proven to impair the multiplication of human astroviruses [121,151]; the effect of natural extracts from the plant Achyrocline bogotensis [152] on astrovirus replication has also been demonstrated, but none of these compounds have been tested in vivo.

8. Conclusions

HAstVs should no longer be considered as only a virus causing mild gastroenteritis in children. Reports of life-threatening CNS infections associated with HAstVs, together with the large panel of host species, their potential broad disease spectrum, and high transmissibility reinforce the hypothesis that astroviruses may emerge and evolve to cause unrecognized diseases in humans. The development of sensitive diagnostic methods, such as broadly reactive reverse transcription quantitative PCR (RTqPCR) assays, of immunological reagents and cell culture-adapted strains should be the next priorities to better understand their evolution and pathogenesis.
On the one hand, HAstVs should still be epidemiologically monitored with special attention to inter-species transmission. Since diagnostic interpretation has gained complexity due to the higher sensitivity of RTqPCR assays, which have been firmly implemented in routine diagnostics, additional case-control studies would be valuable to evaluate whether there is a correlation between viral load and symptoms and assess the role of asymptomatically infected individuals as a virus reservoir. Disease correlation and quantitative analyses should also be performed in case of mixed infections. On the other hand, HAstVs should also be monitored in immunocompromised patients with CNS infection of unknown etiology: definitive diagnosis is crucial to better estimate the burden of HAstV in unexplained infectious encephalitis, and to identify potential modifiable risk factors that could be important for prevention.

Acknowledgments

This work was supported in part by Food-FP7-311846 (European Union) and the Generalitat de Catalunya Biotechnology Reference Network (XRB). We also thank the AGAUR (2014SGR174).

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Appleton, H.; Higgins, P.G. Letter: Viruses and gastroenteritis in infants. Lancet 1975, 1, 1297. [Google Scholar] [CrossRef]
  2. Bosch, A.; Pinto, R.M.; Guix, S. Human astroviruses. Clin. Microbiol. Rev. 2014, 27, 1048–1074. [Google Scholar] [CrossRef] [PubMed]
  3. Mendez, E.; Arias, C.F. Astroviruses. In Fields Virology; Knipe, D.M., Howley, P.M., Eds.; Lippincott Williams and Wilkins: Philadelphia, PA, USA, 2007; Volume 5, pp. 981–1000. [Google Scholar]
  4. Jarchow-Macdonald, A.A.; Halley, S.; Chandler, D.; Gunson, R.; Shepherd, S.J.; Parcell, B.J. First report of an astrovirus type 5 gastroenteritis outbreak in a residential elderly care home identified by sequencing. J. Clin. Virol. 2015, 73, 115–119. [Google Scholar] [CrossRef] [PubMed]
  5. Grohmann, G.S.; Glass, R.I.; Pereira, H.G.; Monroe, S.S.; Hightower, A.W.; Weber, R.; Bryan, R.T. Enteric viruses and diarrhea in HIV-infected patients. N. Engl. J. Med. 1993, 329, 14–20. [Google Scholar] [CrossRef] [PubMed]
  6. Liste, M.B.; Natera, I.; Suarez, J.A.; Pujol, F.H.; Liprandi, F.; Ludert, J.E. Enteric virus infections and diarrhea in healthy and human immunodeficiency virus-infected children. J. Clin. Microbiol. 2000, 38, 2873–2877. [Google Scholar] [PubMed]
  7. Rossit, A.R.; de Almeida, M.T.; Nogueira, C.A.; da Costa Oliveira, J.G.; Barbosa, D.M.; Moscardini, A.C.; Mascarenhas, J.D.; Gabbay, Y.B.; Marques, F.R.; Cardoso, L.V.; et al. Bacterial, yeast, parasitic, and viral enteropathogens in HIV-infected children from Sao Paulo state, Southeastern Brazil. Diagn. Microbiol. Infect. Dis. 2007, 57, 59–66. [Google Scholar] [CrossRef] [PubMed]
  8. Osborne, C.M.; Montano, A.C.; Robinson, C.C.; Schultz-Cherry, S.; Dominguez, S.R. Viral gastroenteritis in children in Colorado 2006–2009. J. Med. Virol. 2015, 87, 931–939. [Google Scholar] [CrossRef] [PubMed]
  9. Finkbeiner, S.R.; Allred, A.F.; Tarr, P.I.; Klein, E.J.; Kirkwood, C.D.; Wang, D. Metagenomic analysis of human diarrhea: Viral detection and discovery. PLoS Pathog. 2008, 4, e1000011. [Google Scholar] [CrossRef] [PubMed]
  10. Finkbeiner, S.R.; Kirkwood, C.D.; Wang, D. Complete genome sequence of a highly divergent astrovirus isolated from a child with acute diarrhea. Virol. J. 2008, 5, 117. [Google Scholar] [CrossRef] [PubMed]
  11. Finkbeiner, S.R.; Li, Y.; Ruone, S.; Conrardy, C.; Gregoricus, N.; Toney, D.; Virgin, H.W.; Anderson, L.J.; Vinje, J.; Wang, D.; et al. Identification of a novel astrovirus (astrovirus VA1) associated with an outbreak of acute gastroenteritis. J. Virol. 2009, 83, 10836–10839. [Google Scholar] [CrossRef] [PubMed]
  12. Finkbeiner, S.R.; Holtz, L.R.; Jiang, Y.; Rajendran, P.; Franz, C.J.; Zhao, G.; Kang, G.; Wang, D. Human stool contains a previously unrecognized diversity of novel astroviruses. Virol. J. 2009, 6, 161. [Google Scholar] [CrossRef] [PubMed]
  13. Finkbeiner, S.R.; Le, B.M.; Holtz, L.R.; Storch, G.A.; Wang, D. Detection of newly described astrovirus MLB1 in stool samples from children. Emerg. Infect. Dis. 2009, 15, 441–444. [Google Scholar] [CrossRef] [PubMed]
  14. Kapoor, A.; Li, L.; Victoria, J.; Oderinde, B.; Mason, C.; Pandey, P.; Zaidi, S.Z.; Delwart, E. Multiple novel astrovirus species in human stool. J. Gen. Virol. 2009, 90, 2965–2972. [Google Scholar] [CrossRef] [PubMed]
  15. Vu, D.L.; Cordey, S.; Brito, F.; Kaiser, L. Novel human astroviruses: Novel human diseases? J. Clin. Virol. 2016, 82, 56–63. [Google Scholar] [CrossRef] [PubMed]
  16. Martella, V.; Pinto, P.; Tummolo, F.; De Grazia, S.; Giammanco, G.M.; Medici, M.C.; Ganesh, B.; L'Homme, Y.; Farkas, T.; Jakab, F.; et al. Analysis of the ORF2 of human astroviruses reveals lineage diversification, recombination and rearrangement and provides the basis for a novel sub-classification system. Arch. Virol. 2014, 159, 3185–3196. [Google Scholar] [CrossRef] [PubMed]
  17. Medici, M.C.; Tummolo, F.; Martella, V.; Banyai, K.; Bonerba, E.; Chezzi, C.; Arcangeletti, M.C.; De Conto, F.; Calderaro, A. Genetic heterogeneity and recombination in type-3 human astroviruses. Infect. Genet. Evol. 2015, 32, 156–160. [Google Scholar] [CrossRef] [PubMed]
  18. Kroneman, A.; Vega, E.; Vennema, H.; Vinje, J.; White, P.A.; Hansman, G.; Green, K.; Martella, V.; Katayama, K.; Koopmans, M. Proposal for a unified norovirus nomenclature and genotyping. Arch. Virol. 2013, 158, 2059–2068. [Google Scholar] [CrossRef] [PubMed]
  19. Jiang, H.; Holtz, L.R.; Bauer, I.; Franz, C.J.; Zhao, G.; Bodhidatta, L.; Shrestha, S.K.; Kang, G.; Wang, D. Comparison of novel MLB-clade, VA-clade and classic human astroviruses highlights constrained evolution of the classic human astrovirus nonstructural genes. Virology 2013, 436, 8–14. [Google Scholar] [CrossRef] [PubMed]
  20. Meyer, C.T.; Bauer, I.K.; Antonio, M.; Adeyemi, M.; Saha, D.; Oundo, J.O.; Ochieng, J.B.; Omore, R.; Stine, O.C.; Wang, D.; et al. Prevalence of classic, MLB-clade and VA-clade astroviruses in Kenya and the Gambia. Virol. J. 2015, 12, 78. [Google Scholar] [CrossRef] [PubMed]
  21. Phan, T.G.; Nordgren, J.; Ouermi, D.; Simpore, J.; Nitiema, L.W.; Deng, X.; Delwart, E. New astrovirus in human feces from Burkina Faso. J. Clin. Virol. 2014, 60, 161–164. [Google Scholar] [CrossRef] [PubMed]
  22. De Benedictis, P.; Schultz-Cherry, S.; Burnham, A.; Cattoli, G. Astrovirus infections in humans and animals—Molecular biology, genetic diversity, and interspecies transmissions. Infect. Genet. Evol. 2011, 11, 1529–1544. [Google Scholar] [CrossRef] [PubMed]
  23. Ulloa, J.C.; Gutierrez, M.F. Genomic analysis of two ORF2 segments of new porcine astrovirus isolates and their close relationship with human astroviruses. Can. J. Microbiol. 2010, 56, 569–577. [Google Scholar] [CrossRef] [PubMed]
  24. Woo, P.C.; Lau, S.K.; Teng, J.L.; Tsang, A.K.; Joseph, S.; Xie, J.; Jose, S.; Fan, R.Y.; Wernery, U.; Yuen, K.Y. A novel astrovirus from dromedaries in the Middle East. J. Gen. Virol. 2015, 96, 2697–2707. [Google Scholar] [CrossRef] [PubMed]
  25. Chen, X.; Zhang, B.; Yue, H.; Wang, Y.; Zhou, F.; Zhang, Q.; Tang, C. A novel astrovirus species in the gut of yaks with diarrhoea in the Qinghai-Tibetan Plateau, 2013. J. Gen. Virol. 2015, 96, 3672–3680. [Google Scholar] [CrossRef] [PubMed]
  26. Hu, B.; Chmura, A.A.; Li, J.; Zhu, G.; Desmond, J.S.; Zhang, Y.; Zhang, W.; Epstein, J.H.; Daszak, P.; Shi, Z. Detection of diverse novel astroviruses from small mammals in China. J. Gen. Virol. 2014, 95, 2442–2449. [Google Scholar] [CrossRef] [PubMed]
  27. Tamura, K.; Stecher, G.; Peterson, D.; Filipski, A.; Kumar, S. MEGA6: Molecular evolutionary genetics analysis version 6.0. Mol. Biol. Evol. 2013, 30, 2725–2729. [Google Scholar] [CrossRef] [PubMed]
  28. Battisti, C.; Salviato, A.; Jonassen, C.; Toffan, A.; Capua, I.; Cattoli, G. Genetic characterization of astroviruses detected in guinea fowl (Numida meleagris) reveals a distinct genotype and suggests cross-species transmission between turkey and guinea fowl. Arch. Virol. 2012, 157, 1329–1337. [Google Scholar] [CrossRef] [PubMed]
  29. Karlsson, E.A.; Small, C.T.; Freiden, P.; Feeroz, M.M.; Matsen, F.A.t.; San, S.; Hasan, M.K.; Wang, D.; Jones-Engel, L.; Schultz-Cherry, S. Non-Human primates harbor diverse mammalian and avian astroviruses including those associated with human infections. PLoS Pathog. 2015, 11, e1005225. [Google Scholar] [CrossRef] [PubMed]
  30. Meliopoulos, V.A.; Kayali, G.; Burnham, A.; Oshansky, C.M.; Thomas, P.G.; Gray, G.C.; Beck, M.A.; Schultz-Cherry, S. Detection of antibodies against turkey astrovirus in humans. PLoS ONE 2014, 9, e96934. [Google Scholar] [CrossRef] [PubMed]
  31. Oude Munnink, B.B.; Cotten, M.; Canuti, M.; Deijs, M.; Jebbink, M.F.; van Hemert, F.J.; Phan, M.V.T.; Bakker, M.; Jazaeri Farsani, S.M.; Kellam, P.; et al. A novel astrovirus-like RNA virus detected in human stool. Virus Evol. 2016, 2, vew005. [Google Scholar] [CrossRef] [PubMed]
  32. Meliopoulos, V.A.; Marvin, S.A.; Freiden, P.; Moser, L.A.; Nighot, P.; Ali, R.; Blikslager, A.; Reddivari, M.; Heath, R.J.; Koci, M.D.; et al. Oral administration of astrovirus capsid protein is sufficient to induce acute diarrhea in vivo. mBio 2016, 7, e01494-16. [Google Scholar] [CrossRef] [PubMed]
  33. Moser, L.A.; Carter, M.; Schultz-Cherry, S. Astrovirus increases epithelial barrier permeability independently of viral replication. J. Virol. 2007, 81, 11937–11945. [Google Scholar] [CrossRef] [PubMed]
  34. Bagci, S.; Eis-Hubinger, A.M.; Yassin, A.F.; Simon, A.; Bartmann, P.; Franz, A.R.; Mueller, A. Clinical characteristics of viral intestinal infection in preterm and term neonates. Eur. J. Clin. Microbiol. Infect. Dis. 2010, 29, 1079–1084. [Google Scholar] [CrossRef] [PubMed]
  35. Chappe, C.; Minjolle, S.; Dabadie, A.; Morel, L.; Colimon, R.; Pladys, P. Astrovirus and digestive disorders in neonatal units. Acta Paediatr. 2012, 101, e208–e212. [Google Scholar] [CrossRef] [PubMed]
  36. Holtz, L.R.; Bauer, I.K.; Rajendran, P.; Kang, G.; Wang, D. Astrovirus MLB1 is not associated with diarrhea in a cohort of Indian children. PLoS ONE. 2011, 6, e28647. [Google Scholar] [CrossRef] [PubMed]
  37. Kapusinszky, B.; Minor, P.; Delwart, E. Nearly constant shedding of diverse enteric viruses by two healthy infants. J. Clin. Microbiol. 2012, 50, 3427–3434. [Google Scholar] [CrossRef] [PubMed]
  38. Resque, H.R.; Munford, V.; Castilho, J.G.; Schmich, H.; Caruzo, T.A.; Racz, M.L. Molecular characterization of astrovirus in stool samples from children in Sao Paulo, Brazil. Mem. Inst. Oswaldo Cruz 2007, 102, 969–974. [Google Scholar] [CrossRef] [PubMed]
  39. Chhabra, P.; Payne, D.C.; Szilagyi, P.G.; Edwards, K.M.; Staat, M.A.; Shirley, S.H.; Wikswo, M.; Nix, W.A.; Lu, X.; Parashar, U.D.; et al. Etiology of viral gastroenteritis in children <5 years of age in the United States, 2008–2009. J. Infect. Dis. 2013, 208, 790–800. [Google Scholar] [PubMed]
  40. Moser, L.A.; Schultz-Cherry, S. Pathogenesis of astrovirus infection. Viral Immunol. 2005, 18, 4–10. [Google Scholar] [CrossRef] [PubMed]
  41. Wunderli, W.; Meerbach, A.; Gungor, T.; Berger, C.; Greiner, O.; Caduff, R.; Trkola, A.; Bossart, W.; Gerlach, D.; Schibler, M.; et al. Astrovirus infection in hospitalized infants with severe combined immunodeficiency after allogeneic hematopoietic stem cell transplantation. PLoS ONE 2011, 6, e27483. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  42. Mor, S.K.; Abin, M.; Costa, G.; Durrani, A.; Jindal, N.; Goyal, S.M.; Patnayak, D.P. The role of type-2 turkey astrovirus in poult enteritis syndrome. Poult. Sci. 2011, 90, 2747–2752. [Google Scholar] [CrossRef] [PubMed]
  43. Schroeder, B.O.; Backhed, F. Signals from the gut microbiota to distant organs in physiology and disease. Nat. Med. 2016, 22, 1079–1089. [Google Scholar] [CrossRef] [PubMed]
  44. Pativada, M.; Nataraju, S.M.; Ganesh, B.; Rajendran, K.; Ramamurthy, T.; Ganguly, S.; Bhattacharya, M.K.; Ghosh, M.; Kobayashi, N.; Krishnan, T. Emerging trends in the epidemiology of human astrovirus infection among infants, children and adults hospitalized with acute watery diarrhea in Kolkata, India. Infect. Genet. Evol. 2012, 12, 1685–1693. [Google Scholar] [CrossRef]
  45. Pfeiffer, J.K.; Virgin, H.W. Viral immunity. Transkingdom control of viral infection and immunity in the mammalian intestine. Science 2016, 351, 6270. [Google Scholar] [CrossRef] [PubMed]
  46. Qureshi, M.A.; Saif, Y.M.; Heggen-Peay, C.L.; Edens, F.W.; Havenstein, G.B. Induction of functional defects in macrophages by a poult enteritis and mortality syndrome-associated turkey astrovirus. Avian Dis. 2001, 45, 853–861. [Google Scholar] [CrossRef] [PubMed]
  47. Quan, P.L.; Wagner, T.A.; Briese, T.; Torgerson, T.R.; Hornig, M.; Tashmukhamedova, A.; Firth, C.; Palacios, G.; Baisre-De-Leon, A.; Paddock, C.D.; et al. Astrovirus encephalitis in boy with X-linked agammaglobulinemia. Emerg. Infect. Dis. 2010, 16, 918–925. [Google Scholar] [CrossRef] [PubMed]
  48. Brown, J.R.; Morfopoulou, S.; Hubb, J.; Emmett, W.A.; Ip, W.; Shah, D.; Brooks, T.; Paine, S.M.; Anderson, G.; Virasami, A.; et al. Astrovirus VA1/HMO-C: An increasingly recognized neurotropic pathogen in immunocompromised patients. Clin. Infect. Dis. 2015, 60, 881–888. [Google Scholar] [CrossRef] [PubMed]
  49. Naccache, S.N.; Peggs, K.S.; Mattes, F.M.; Phadke, R.; Garson, J.A.; Grant, P.; Samayoa, E.; Federman, S.; Miller, S.; Lunn, M.P.; et al. Diagnosis of neuroinvasive astrovirus infection in an immunocompromised adult with encephalitis by unbiased next-generation sequencing. Clin. Infect. Dis. 2015, 60, 919–923. [Google Scholar] [CrossRef] [PubMed]
  50. Fremond, M.L.; Perot, P.; Muth, E.; Cros, G.; Dumarest, M.; Mahlaoui, N.; Seilhean, D.; Desguerre, I.; Hebert, C.; Corre-Catelin, N.; et al. Next-Generation sequencing for diagnosis and tailored therapy: A case report of astrovirus-associated progressive encephalitis. J. Pediatric. Infect. Dis. Soc. 2015, 4, e53–e57. [Google Scholar] [CrossRef] [PubMed]
  51. Lum, S.H.; Turner, A.; Guiver, M.; Bonney, D.; Martland, T.; Davies, E.; Newbould, M.; Brown, J.; Morfopoulou, S.; Breuer, J.; et al. An emerging opportunistic infection: Fatal astrovirus (VA1/HMO-C) encephalitis in a pediatric stem cell transplant recipient. Transpl. Infect. Dis. 2016. [Google Scholar] [CrossRef] [PubMed]
  52. Cordey, S.; Vu, D.-L.; Schibler, M.; L'Huillier, A.G.; Brito, F.; Docquier, M.; Posfay-Barbe, K.M.; Petty, T.J.; Turin, L.; Zdobnov, E.M.; et al. Astrovirus MLB2: A new gastro-enteric virus associated with meningitis and disseminated infection. Emerg. Infect. Dis. 2016, 22, 846–853. [Google Scholar] [CrossRef] [PubMed]
  53. Sato, M.; Kuroda, M.; Kasai, M.; Matsui, H.; Fukuyama, T.; Katano, H.; Tanaka-Taya, K. Acute encephalopathy in an immunocompromised boy with astrovirus-MLB1 infection detected by next generation sequencing. J. Clin. Virol. 2016, 78, 66–70. [Google Scholar] [CrossRef] [PubMed]
  54. Wuthrich, D.; Boujon, C.L.; Truchet, L.; Selimovic-Hamza, S.; Oevermann, A.; Bouzalas, I.G.; Bruggmann, R.; Seuberlich, T. Exploring the virome of cattle with non-suppurative encephalitis of unknown etiology by metagenomics. Virology 2016, 493, 22–30. [Google Scholar] [CrossRef] [PubMed]
  55. Blomstrom, A.L.; Widen, F.; Hammer, A.S.; Belak, S.; Berg, M. Detection of a novel astrovirus in brain tissue of mink suffering from shaking mink syndrome by use of viral metagenomics. J. Clin. Microbiol. 2010, 48, 4392–4396. [Google Scholar] [CrossRef] [PubMed]
  56. Blomstrom, A.L.; Ley, C.; Jacobson, M. Astrovirus as a possible cause of congenital tremor type AII in piglets? Acta Vet. Scand. 2014, 56, 82. [Google Scholar] [CrossRef] [PubMed]
  57. Wood, D.J.; David, T.J.; Chrystie, I.L.; Totterdell, B. Chronic enteric virus infection in two T-cell immunodeficient children. J. Med. Virol. 1988, 24, 435–444. [Google Scholar] [CrossRef] [PubMed]
  58. Yokoyama, C.C.; Loh, J.; Zhao, G.; Stappenbeck, T.S.; Wang, D.; Huang, H.V.; Virgin, H.W.; Thackray, L.B. Adaptive immunity restricts replication of novel murine astroviruses. J. Virol. 2012, 86, 12262–12270. [Google Scholar] [CrossRef] [PubMed]
  59. Koopmans, M.P.; Bijen, M.H.; Monroe, S.S.; Vinje, J. Age-Stratified seroprevalence of neutralizing antibodies to astrovirus types 1 to 7 in humans in the Netherlands. Clin. Diagn. Lab. Immunol. 1998, 5, 33–37. [Google Scholar] [PubMed]
  60. Guix, S.; Pérez-Bosque, A.; Miró, L.; Moretó, M.; Bosch, A.; Pintó, R.M. Type I interferon response is delayed in human astrovirus infections. PLoS ONE 2015, 10, e0123087. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  61. Marvin, S.A.; Huerta, C.T.; Sharp, B.; Freiden, P.; Cline, T.D.; Schultz-Cherry, S. Type I interferon response limits astrovirus replication and protects against increased barrier permeability in vitro and in vivo. J. Virol. 2015, 90, 1988–1996. [Google Scholar] [CrossRef] [PubMed]
  62. Koci, M.D.; Kelley, L.A.; Larsen, D.; Schultz-Cherry, S. Astrovirus-Induced synthesis of nitric oxide contributes to virus control during infection. J. Virol. 2004, 78, 1564–1574. [Google Scholar] [CrossRef] [PubMed]
  63. Holtz, L.R.; Wylie, K.M.; Sodergren, E.; Jiang, Y.; Franz, C.J.; Weinstock, G.M.; Storch, G.A.; Wang, D. Astrovirus MLB2 viremia in febrile child. Emerg. Infect. Dis. 2011, 17, 2050–2052. [Google Scholar] [CrossRef] [PubMed]
  64. Wylie, K.M.; Mihindukulasuriya, K.A.; Sodergren, E.; Weinstock, G.M.; Storch, G.A. Sequence analysis of the human virome in febrile and afebrile children. PLoS ONE 2012, 7, e27735. [Google Scholar] [CrossRef] [PubMed]
  65. Cordey, S.; Brito, F.; Vu, D.L.; Turin, L.; Kilowoko, M.; Kyungu, E.; Genton, B.; Zdobnov, E.M.; D'Acremont, V.; Kaiser, L. Astrovirus VA1 identified by next-generation sequencing in a nasopharyngeal specimen of a febrile tanzanian child with acute respiratory disease of unknown etiology. Emerg. Microbes Infect. 2016, 5, e99. [Google Scholar] [CrossRef] [PubMed]
  66. Meliopoulos, V.; Schultz-Cherry, S. Astrovirus pathogenesis. In Astrovirus Research: Essential Ideas, Everyday Impacts, Future Directions; Schultz-Cherry, S., Ed.; Springer: New York, NY, USA, 2013; pp. 65–77. [Google Scholar]
  67. Pantin-Jackwood, M.; Todd, D.; Koci, M.D. Avian astroviruses. In Astrovirus Research: Essential Ideas, Everyday Impacts, Future Directions; Schultz-Cherry, S., Ed.; Springer: New York, NY, USA, 2013; pp. 151–180. [Google Scholar]
  68. Wang, Y.; Li, Y.; Jin, Y.; Li, D.D.; Li, X.; Duan, Z.J. Recently identified novel human astroviruses in children with diarrhea, China. Emerg. Infect. Dis. 2013, 19, 1333–1335. [Google Scholar] [CrossRef] [PubMed]
  69. Xavier, M.d.P.T.P.; Carvalho Costa, F.A.; Rocha, M.S.; Andrade, J.d.S.R.d.; Diniz, F.K.B.; Andrade, T.R.d.; Miagostovich, M.P.; Leite, J.P.G.; Volotão, E.d.M. Surveillance of human astrovirus infection in Brazil: The first report of MLB1 astrovirus. PLoS ONE 2015, 10, e0135687. [Google Scholar] [CrossRef] [PubMed]
  70. Galdiero, E.; Marinelli, A.; Pisciotta, M.G.; Pagliara, I.; Di Monteforte, E.S.; Liguori, G. Reverse transcriptase-PCR for the detection of astrovirus in children with nosocomial acute diarrhoea in Naples, Italy. Méd. Mal. Infect. 2005, 35, 213–217. [Google Scholar] [CrossRef] [PubMed]
  71. Nigel, A.C.; Booth, J.A.; Claire, E.; Sharon, J.L.; Will, S.; Nick, K.; Osamu, N.; Toyoko, N.; Hart, C.A.; Martyn, R. Healthcare-Associated viral gastroenteritis among children in a large pediatric hospital, United Kingdom. Emerg. Infect. Dis. J 2010, 16, 55. [Google Scholar]
  72. Nguyen, T.A.; Yagyu, F.; Okame, M.; Phan, T.G.; Trinh, Q.D.; Yan, H.; Hoang, K.T.; Cao, A.T.; Le Hoang, P.; Okitsu, S.; et al. Diversity of viruses associated with acute gastroenteritis in children hospitalized with diarrhea in Ho Chi Minh city, Vietnam. J. Med. Virol. 2007, 79, 582–590. [Google Scholar] [CrossRef] [PubMed]
  73. Rimoldi, S.G.; Stefani, F.; Pagani, C.; Chenal, L.L.; Zanchetta, N.; Di Bartolo, I.; Lombardi, A.; Ruggeri, F.M.; Di lillo, D.; Zuccotti, G.V.; et al. Epidemiological and clinical characteristics of pediatric gastroenteritis associated with new viral agents. Arch. Virol. 2011, 156, 1583. [Google Scholar] [CrossRef] [PubMed]
  74. Al-Thani, A.; Baris, M.; Al-Lawati, N.; Al-Dhahry, S. Characterising the aetiology of severe acute gastroenteritis among patients visiting a hospital in Qatar using real-time polymerase chain reaction. BMC Infect. Dis. 2013, 13, 329. [Google Scholar] [CrossRef] [PubMed]
  75. Gonzalez, G.G.; Liprandi, F.; Ludert, J.E. Molecular epidemiology of enteric viruses in children with sporadic gastroenteritis in Valencia, Venezuela. J. Med. Virol. 2011, 83, 1972–1982. [Google Scholar] [CrossRef] [PubMed]
  76. Wang, F.; Wang, Y.-H.; Peng, J.-S.; Zhou, X.; Tang, L.; Kobayashi, N.; Hu, Q.; Zhou, D.-J.; Huang, H.-J.; Liu, M.-Q. Genetic characterization of human astrovirus infection in Wuhan, People’s Republic of China, 2007–2008. Can. J. Microbiol. 2011, 57, 964–968. [Google Scholar] [CrossRef] [PubMed]
  77. Ouyang, Y.; Ma, H.; Jin, M.; Wang, X.; Wang, J.; Xu, L.; Lin, S.; Shen, Z.; Chen, Z.; Qiu, Z.; et al. Etiology and epidemiology of viral diarrhea in children under the age of five hospitalized in Tianjin, China. Arch. Virol. 2012, 157, 881–887. [Google Scholar] [CrossRef] [PubMed]
  78. Lu, L.; Jia, R.; Zhong, H.; Xu, M.; Su, L.; Cao, L.; Dong, Z.; Dong, N.; Xu, J. Molecular characterization and multiple infections of rotavirus, norovirus, sapovirus, astrovirus and adenovirus in outpatients with sporadic gastroenteritis in Shanghai, China, 2010–2011. Arch. Virol. 2015, 160, 1229–1238. [Google Scholar] [CrossRef] [PubMed]
  79. Dai, Y.-c.; Xu, Q.-h.; Wu, X.-b.; Hu, G.-f.; Tang, Y.-l.; Li, J.-d.; Chen, Q.; Nie, J. Development of real-time and nested RT-PCR to detect astrovirus and one-year survey of astrovirus in Jiangmen city, China. Arch. Virol. 2010, 155, 977–982. [Google Scholar] [CrossRef] [PubMed]
  80. Verma, H.; Chitambar, S.D.; Gopalkrishna, V. Astrovirus associated acute gastroenteritis in western India: Predominance of dual serotype strains. Infect. Genet. Evol. 2010, 10, 575–579. [Google Scholar] [CrossRef] [PubMed]
  81. Thongprachum, A.; Takanashi, S.; Kalesaran, A.F.C.; Okitsu, S.; Mizuguchi, M.; Hayakawa, S.; Ushijima, H. Four-Year study of viruses that cause diarrhea in japanese pediatric outpatients. J. Med. Virol. 2015, 87, 1141–1148. [Google Scholar] [CrossRef] [PubMed]
  82. Yoneda, M.; Nakano, M.; Sugimoto, D.; Inada, M.; Fujitani, M.; Kitahori, Y. Epidemiological characteristics of sapovirus and human astrovirus detected among children in the Nara Prefecture, Japan, during 2009/2010–2014/2015 seasons. Jpn. J. Infect. Dis. 2016, 70, 87–91. [Google Scholar] [CrossRef] [PubMed]
  83. Nakamura, N.; Kobayashi, S.; Minagawa, H.; Matsushita, T.; Sugiura, W.; Iwatani, Y. Molecular epidemiology of enteric viruses in patients with acute gastroenteritis in Aichi Prefecture, Japan, 2008/09−2013/14. J. Med. Virol. 2016, 88, 1180–1186. [Google Scholar] [CrossRef] [PubMed]
  84. Khamrin, P.; Thongprachum, A.; Okitsu, S.; Hayakawa, S.; Maneekarn, N.; Ushijima, H. Multiple astrovirus MLB1, MLB2, VA2 clades, and classic human astrovirus in children with acute gastroenteritis in Japan. J. Med. Virol. 2016, 88, 356–360. [Google Scholar] [CrossRef] [PubMed]
  85. Chen, C.J.; Wu, F.T.; Huang, Y.C.; Chang, W.C.; Wu, H.S.; Wu, C.Y.; Lin, J.S.; Huang, F.C.; Hsiung, C.A. Clinical and epidemiologic features of severe viral gastroenteritis in children: A 3-year surveillance, multicentered study in Taiwan with partial rotavirus immunization. Med. (Baltim.) 2015, 94, e1372. [Google Scholar] [CrossRef] [PubMed]
  86. Malasao, R.; Khamrin, P.; Chaimongkol, N.; Ushijima, H.; Maneekarn, N. Diversity of human astrovirus genotypes circulating in children with acute gastroenteritis in Thailand during 2000–2011. J. Med. Virol. 2012, 84, 1751–1756. [Google Scholar] [CrossRef] [PubMed]
  87. Nguyen, T.A.; Hoang, L.; Pham le, D.; Hoang, K.T.; Mizuguchi, M.; Okitsu, S.; Ushijima, H. Identification of human astrovirus infections among children with acute gastroenteritis in the Southern part of Vietnam during 2005–2006. J. Med. Virol. 2008, 80, 298–305. [Google Scholar] [CrossRef] [PubMed]
  88. Ouédraogo, N.; Kaplon, J.; Bonkoungou, I.J.O.; Traoré, A.S.; Pothier, P.; Barro, N.; Ambert-Balay, K. Prevalence and genetic diversity of enteric viruses in children with diarrhea in Ouagadougou, Burkina Faso. PLoS ONE 2016, 11, e0153652. [Google Scholar] [CrossRef] [PubMed]
  89. Lekana-Douki, S.E.; Kombila-Koumavor, C.; Nkoghe, D.; Drosten, C.; Drexler, J.F.; Leroy, E.M. Molecular epidemiology of enteric viruses and genotyping of rotavirus a, adenovirus and astrovirus among children under 5 years old in Gabon. Int. J. Infect. Dis. 2015, 34, 90–95. [Google Scholar] [CrossRef] [PubMed]
  90. Reither, K.; Ignatius, R.; Weitzel, T.; Seidu-Korkor, A.; Anyidoho, L.; Saad, E.; Djie-Maletz, A.; Ziniel, P.; Amoo-Sakyi, F.; Danikuu, F.; et al. Acute childhood diarrhoea in northern Ghana: Epidemiological, clinical and microbiological characteristics. BMC Infect. Dis. 2007, 7, 104. [Google Scholar] [CrossRef] [PubMed]
  91. Mladenova, Z.; Steyer, A.; Steyer, A.F.; Ganesh, B.; Petrov, P.; Tchervenjakova, T.; Iturriza-Gomara, M. Aetiology of acute paediatric gastroenteritis in Bulgaria during summer months: Prevalence of viral infections. J. Med. Microbiol. 2015, 64, 272–282. [Google Scholar] [CrossRef] [PubMed]
  92. Simonen-Tikka, M.-L.; Klemola, P.; Suomenrinne, S.; Kaijalainen, S.; Söderström, D.; Savolainen-Kopra, C.; Näntö-Salonen, K.; Ilonen, J.; Simell, T.; Simell, O.; et al. Virus infections among young children—The first year of the indis study. J. Med. Virol. 2013, 85, 1678–1684. [Google Scholar] [CrossRef] [PubMed]
  93. Medici, M.C.; Tummolo, F.; Albonetti, V.; Abelli, L.A.; Chezzi, C.; Calderaro, A. Molecular detection and epidemiology of astrovirus, bocavirus, and sapovirus in italian children admitted to hospital with acute gastroenteritis, 2008–2009. J. Med. Virol. 2012, 84, 643–650. [Google Scholar] [CrossRef] [PubMed]
  94. Chhabra, P.; Samoilovich, E.; Yermalovich, M.; Chernyshova, L.; Gheorghita, S.; Cojocaru, R.; Shugayev, N.; Sahakyan, G.; Lashkarashvili, M.; Chubinidze, M.; et al. Viral gastroenteritis in rotavirus negative hospitalized children <5 years of age from the independent states of the former Soviet Union. Infect. Genet. Evol. 2014, 28, 283–288. [Google Scholar] [PubMed]
  95. Gabbay, Y.B.; Luz, C.R.; Costa, I.V.; Cavalcante-Pepino, E.L.; Sousa, M.S.; Oliveira, K.K.; Wanzeller, A.L.; Mascarenhas, J.D.; Leite, J.P.; Linhares, A.C. Prevalence and genetic diversity of astroviruses in children with and without diarrhea in Sao Luis, Maranhao, Brazil. Mem. Inst. Oswaldo Cruz 2005, 100, 709–714. [Google Scholar] [CrossRef] [PubMed]
  96. Santos, R.A.; Borges, A.M.; da Costa, P.S.; Teixeira, J.M.; Giugliano, L.G.; Leite, J.P.; Cardoso, D. Astrovirus infection in children living in the central west region of Brazil. Mem. Inst. Oswaldo Cruz 2007, 102, 209–213. [Google Scholar] [CrossRef] [PubMed]
  97. Liu, L.-J.; Liu, W.; Liu, Y.-X.; Xiao, H.-J.; Jia, N.; Liu, G.; Tong, Y.-G.; Cao, W.-C. Identification of norovirus as the top enteric viruses detected in adult cases with acute gastroenteritis. Am. J. Trop. Med. Hyg. 2010, 82, 717–722. [Google Scholar] [PubMed]
  98. Arena, C.; Amoros, J.P.; Vaillant, V.; Ambert-Balay, K.; Chikhi-Brachet, R.; Jourdan-Da Silva, N.; Varesi, L.; Arrighi, J.; Souty, C.; Blanchon, T.; et al. Acute diarrhea in adults consulting a general practitioner in France during winter: Incidence, clinical characteristics, management and risk factors. BMC Infect. Dis. 2014, 14, 574. [Google Scholar] [CrossRef] [PubMed]
  99. Podkolzin, A.T.; Fenske, E.B.; Abramycheva, N.Y.; Shipulin, G.A.; Sagalova, O.I.; Mazepa, V.N.; Ivanova, G.N.; Semena, A.V.; Tagirova, Z.G.; Alekseeva, M.N.; et al. Hospital-Based surveillance of rotavirus and other viral agents of diarrhea in children and adults in Russia, 2005–2007. J. Infect. Dis. 2009, 200 (Suppl. 1), S228–S233. [Google Scholar] [CrossRef] [PubMed]
  100. Chau, M.L.; Hartantyo, S.H.; Yap, M.; Kang, J.S.; Aung, K.T.; Gutierrez, R.A.; Ng, L.C.; Tam, C.C.; Barkham, T. Diarrheagenic pathogens in adults attending a hospital in Singapore. BMC Infect. Dis. 2016, 16, 32. [Google Scholar] [CrossRef] [PubMed]
  101. Gabbay, Y.B.; Leite, J.P.; Oliveira, D.S.; Nakamura, L.S.; Nunes, M.R.; Mascarenhas, J.D.; Heinemann, M.B.; Linhares, A.C. Molecular epidemiology of astrovirus type 1 in Belem, Brazil, as an agent of infantile gastroenteritis, over a period of 18 years (1982–2000): Identification of two possible new lineages. Virus Res. 2007, 129, 166–174. [Google Scholar] [CrossRef] [PubMed]
  102. De Grazia, S.; Bonura, F.; Bányai, K.; Gellért, Á.; Marineo, S.; Martella, V.; Giammanco, G.M. Temporal variation in the distribution of type-1 human astrovirus lineages in a settled population over 14 years. Arch. Virol. 2016, 161, 1633–1637. [Google Scholar] [CrossRef] [PubMed]
  103. Grant, L.; Vinje, J.; Parashar, U.; Watt, J.; Reid, R.; Weatherholtz, R.; Santosham, M.; Gentsch, J.; O'Brien, K. Epidemiologic and clinical features of other enteric viruses associated with acute gastroenteritis in american indian infants. J. Pediatr. 2012, 161, 110–115; e111. [Google Scholar] [CrossRef] [PubMed]
  104. Platts-Mills, J.A.; Gratz, J.; Mduma, E.; Svensen, E.; Amour, C.; Liu, J.; Maro, A.; Saidi, Q.; Swai, N.; Kumburu, H.; et al. Association between stool enteropathogen quantity and disease in tanzanian children using Taqman array cards: A nested case-control study. Am. J. Trop. Med. Hyg. 2014, 90, 133–138. [Google Scholar] [CrossRef] [PubMed]
  105. Lopman, B.A.; Steele, D.; Kirkwood, C.D.; Parashar, U.D. The vast and varied global burden of norovirus: Prospects for prevention and control. PLoS Med. 2016, 13, e1001999. [Google Scholar] [CrossRef]
  106. Svraka, S.; Duizer, E.; Vennema, H.; de Bruin, E.; van der Veer, B.; Dorresteijn, B.; Koopmans, M. Etiological role of viruses in outbreaks of acute gastroenteritis in the Netherlands from 1994 through 2005. J. Clin. Microbiol. 2007, 45, 1389–1394. [Google Scholar] [CrossRef] [PubMed]
  107. Lyman, W.H.; Walsh, J.F.; Kotch, J.B.; Weber, D.J.; Gunn, E.; Vinje, J. Prospective study of etiologic agents of acute gastroenteritis outbreaks in child care centers. J. Pediatr. 2009, 154, 253–257. [Google Scholar] [CrossRef] [PubMed]
  108. Marshall, J.A.; Bruggink, L.D.; Sturge, K.; Subasinghe, N.; Tan, A.; Hogg, G.G. Molecular features of astrovirus associated with a gastroenteritis outbreak in an aged-care centre. Eur. J. Clin. Microbiol. Infect. Dis. 2007, 26, 67–71. [Google Scholar] [CrossRef] [PubMed]
  109. Oishi, I.; Yamazaki, K.; Kimoto, T.; Minekawa, Y.; Utagawa, E.; Yamazaki, S.; Inouye, S.; Grohmann, G.S.; Monroe, S.S.; Stine, S.E.; et al. A large outbreak of acute gastroenteritis associated with astrovirus among students and teachers in Osaka, Japan. J. Infect. Dis. 1994, 170, 439–443. [Google Scholar] [CrossRef] [PubMed]
  110. van der Doef, H.P.J.; Bathoorn, E.; van der Linden, M.P.M.; Wolfs, T.F.W.; Minderhoud, A.L.C.; Bierings, M.B.; Wensing, A.M.J.; Lindemans, C.A. Astrovirus outbreak at a pediatric hematology and hematopoietic stem cell transplant unit despite strict hygiene rules. Bone Marrow. Transpl. 2016, 51, 747–750. [Google Scholar] [CrossRef] [PubMed]
  111. Li, C.-y.; Liu, N.; Guo, W.-d.; Yu, Q.; Wang, W.-r.; Song, Z.-Z.; Yan, H.; Luo, Y.; Lu, A.-t.; Li, H.-Y.; et al. Outbreak of neonatal gastroenteritis associated with astrovirus serotype 1 at a hospital in Inner Mongolia, China. J. Clin. Microbiol. 2010, 48, 4306–4309. [Google Scholar] [CrossRef] [PubMed]
  112. Sirinavin, S.; Techasaensiri, C.; Okascharoen, C.; Nuntnarumit, P.; Tonsuttakul, S.; Pongsuwan, Y. Neonatal astrovirus gastroenteritis during an inborn nursery outbreak. J. Hosp. Infect. 2006, 64, 196–197. [Google Scholar] [CrossRef] [PubMed]
  113. Hwang, B.J.S.; Jeong, H.J.; Chung, G.T.; Kang, Y.; Yang, S.J.; Seo, N.Y.; Shin, T.H.; Yoo, C.; Lee, D.Y. Outbreak of astrovirus in adults with acute gastroenteritis in Korea. J. Gastrointest. Dig. Syst. 2015, S13. [Google Scholar] [CrossRef]
  114. Burbelo, P.D.; Ching, K.H.; Esper, F.; Iadarola, M.J.; Delwart, E.; Lipkin, W.I.; Kapoor, A. Serological studies confirm the novel astrovirus HMOAstV-C as a highly prevalent human infectious agent. PLoS ONE 2011, 6, e22576. [Google Scholar] [CrossRef] [PubMed]
  115. Holtz, L.R.; Bauer, I.K.; Jiang, H.; Belshe, R.; Freiden, P.; Schultz-Cherry, S.L.; Wang, D. Seroepidemiology of astrovirus MLB1. Clin. Vaccine Immunol. 2014, 21, 908–911. [Google Scholar] [CrossRef] [PubMed]
  116. Chu, D.K.W.; Chin, A.W.H.; Smith, G.J.; Chan, K.-H.; Guan, Y.; Peiris, J.S.M.; Poon, L.L.M. Detection of novel astroviruses in urban brown rats and previously known astroviruses in humans. J. Gen. Virol. 2010, 91, 2457–2462. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  117. Ahmed, S.F.; Sebeny, P.J.; Klena, J.D.; Pimentel, G.; Mansour, A.; Naguib, A.M.; Bruton, J.; Young, S.Y.; Holtz, L.R.; Wang, D. Novel astroviruses in children, Egypt. Emerg. Infect. Dis. 2011, 17, 2391–2393. [Google Scholar] [CrossRef] [PubMed]
  118. Mitui, M.T.; Bozdayi, G.; Matsumoto, T.; Dalgic, B.; Nishizono, A.; Ahmed, K. Complete genome sequence of an MLB2 astrovirus from a turkish child with diarrhea. Genome Announc. 2013, 1. [Google Scholar] [CrossRef] [PubMed]
  119. Midthun, K.; Greenberg, H.B.; Kurtz, J.B.; Gary, G.W.; Lin, F.Y.; Kapikian, A.Z. Characterization and seroepidemiology of a type 5 astrovirus associated with an outbreak of gastroenteritis in Marin County, California. J. Clin. Microbiol. 1993, 31, 955–962. [Google Scholar] [PubMed]
  120. Kurtz, J.B.; Lee, T.W.; Craig, J.W.; Reed, S.E. Astrovirus infection in volunteers. J. Med. Virol. 1979, 3, 221–230. [Google Scholar] [CrossRef] [PubMed]
  121. Abad, F.X.; Pinto, R.M.; Villena, C.; Gajardo, R.; Bosch, A. Astrovirus survival in drinking water. Appl. Environ. Microbiol. 1997, 63, 3119–3122. [Google Scholar] [PubMed]
  122. Bosch, A.; Pinto, R.M.; Villena, C.; Abad, F.X. Persistence of human astrovirus in fresh and marine water. Water Sci. Technol. 1997, 35, 243–247. [Google Scholar] [CrossRef]
  123. Pintó, R.M.; Villena, C.; Le Guyader, F.; Guix, S.; Caballero, S.; Pommepuy, M.; Bosch, A. Astrovirus detection in wastewater samples. Water Sci. Technol. 2001, 43, 73–76. [Google Scholar] [PubMed]
  124. Le Cann, P.; Ranarijaona, S.; Monpoeho, S.; Le Guyader, F.; Ferre, V. Quantification of human astroviruses in sewage using real-time RT-PCR. Res. Microbiol. 2004, 155, 11–15. [Google Scholar] [CrossRef] [PubMed]
  125. El-Senousy, W.M.; Guix, S.; Abid, I.; Pinto, R.M.; Bosch, A. Removal of astrovirus from water and sewage treatment plants, evaluated by a competitive reverse transcription-PCR. Appl. Environ. Microbiol. 2007, 73, 164–167. [Google Scholar] [CrossRef] [PubMed]
  126. Prevost, B.; Lucas, F.S.; Ambert-Balay, K.; Pothier, P.; Moulin, L.; Wurtzer, S. Deciphering the diversities of astroviruses and noroviruses in wastewater treatment plant effluents by a high-throughput sequencing method. Appl. Environ. Microbiol. 2015, 81, 7215–7222. [Google Scholar] [CrossRef] [PubMed]
  127. Lizasoain, A.; Tort, L.F.; Garcia, M.; Gomez, M.M.; Leite, J.P.; Miagostovich, M.P.; Cristina, J.; Colina, R.; Victoria, M. Environmental assessment reveals the presence of MLB-1 human astrovirus in Uruguay. J. Appl. Microbiol. 2015, 119, 859–867. [Google Scholar] [CrossRef] [PubMed]
  128. Hata, A.; Katayama, H.; Kitajima, M.; Furumai, H. Wastewater analysis indicates that genetically diverse astroviruses, including strains belonging to novel clades MLB and VA, are circulating within Japanese populations. Appl. Environ. Microbiol. 2015, 81, 4932–4939. [Google Scholar] [CrossRef] [PubMed]
  129. Le Guyader, F.; Haugarreau, L.; Miossec, L.; Dubois, E.; Pommepuy, M. Three-Year study to assess human enteric viruses in shellfish. Appl. Environ. Microbiol. 2000, 66, 3241–3248. [Google Scholar] [CrossRef] [PubMed]
  130. Nadan, S.; Walter, J.E.; Grabow, W.O.; Mitchell, D.K.; Taylor, M.B. Molecular characterization of astroviruses by reverse transcriptase PCR and sequence analysis: Comparison of clinical and environmental isolates from South Africa. Appl. Environ. Microbiol. 2003, 69, 747–753. [Google Scholar] [CrossRef] [PubMed]
  131. Pintó, R.M.; Abad, F.X.; Gajardo, R.; Bosch, A. Detection of infectious astroviruses in water. Appl. Environ. Microbiol. 1996, 62, 1811–1813. [Google Scholar] [PubMed]
  132. World Health Organization (WHO). Guidelines for Drinking-Water Quality, Volume 1: Recommendations, 3rd ed.; WHO: Geneva, Switzerland, 2004; p. 515. [Google Scholar]
  133. Gofti-Laroche, L.; Gratacap-Cavallier, B.; Demanse, D.; Genoulaz, O.; Seigneurin, J.M.; Zmirou, D. Are waterborne astrovirus implicated in acute digestive morbidity (E.MI.R.A. Study)? J. Clin. Virol. 2003, 27, 74–82. [Google Scholar] [CrossRef]
  134. Dongdem, J.T.; Damanka, S.; Asmah, R. Molecular isolation of human norovirus and astrovirus in tap water by RT-PCR. Int. Res. J. Biochem. Bioinform. 2011, 1, 131–138. [Google Scholar]
  135. Steyer, A.; Torkar, K.G.; Gutiérrez-Aguirre, I.; Poljšak-Prijatelj, M. High prevalence of enteric viruses in untreated individual drinking water sources and surface water in Slovenia. Int. J. Hyg. Environ. Health 2011, 214, 392–398. [Google Scholar] [CrossRef] [PubMed]
  136. Myint, S.; Manley, R.; Cubitt, D. Viruses in bathing waters. Lancet 1994, 343, 1640–1641. [Google Scholar] [CrossRef]
  137. Maunula, L.; Kalso, S.; von Bonsdorff, C.H.; Ponka, A. Wading pool water contaminated with both noroviruses and astroviruses as the source of a gastroenteritis outbreak. Epidemiol. Infect. 2004, 132, 737–743. [Google Scholar] [CrossRef] [PubMed]
  138. Mendez-Toss, M.; Griffin, D.D.; Calva, J.; Contreras, J.F.; Puerto, F.I.; Mota, F.; Guiscafre, H.; Cedillo, R.; Munoz, O.; Herrera, I.; et al. Prevalence and genetic diversity of human astroviruses in mexican children with symptomatic and asymptomatic infections. J. Clin. Microbiol. 2004, 42, 151–157. [Google Scholar] [CrossRef] [PubMed]
  139. Herrmann, J.E.; Taylor, D.N.; Echeverria, P.; Blacklow, N.R. Astroviruses as a cause of gastroenteritis in children. N. Engl. J. Med. 1991, 324, 1757–1760. [Google Scholar] [CrossRef] [PubMed]
  140. Konno, T.; Suzuki, H.; Ishida, N.; Chiba, R.; Mochizuki, K.; Tsunoda, A. Astrovirus-Associated epidemic gastroenteritis in Japan. J. Med. Virol. 1982, 9, 11–17. [Google Scholar] [CrossRef] [PubMed]
  141. Todd, E.C.; Greig, J.D.; Bartleson, C.A.; Michaels, B.S. Outbreaks where food workers have been implicated in the spread of foodborne disease. Part 3. Factors contributing to outbreaks and description of outbreak categories. J. Food Prot. 2007, 70, 2199–2217. [Google Scholar] [CrossRef] [PubMed]
  142. Gallimore, C.I.; Taylor, C.; Gennery, A.R.; Cant, A.J.; Galloway, A.; Lewis, D.; Gray, J.J. Use of a heminested reverse transcriptase PCR assay for detection of astrovirus in environmental swabs from an outbreak of gastroenteritis in a pediatric primary immunodeficiency unit. J. Clin. Microbiol. 2005, 43, 3890–3894. [Google Scholar] [CrossRef] [PubMed]
  143. Cubitt, W.D.; Mitchell, D.K.; Carter, M.J.; Willcocks, M.M.; Holzel, H. Application of electronmicroscopy, enzyme immunoassay, and RT-PCR to monitor an outbreak of astrovirus type 1 in a paediatric bone marrow transplant unit. J. Med. Virol. 1999, 57, 313–321. [Google Scholar] [CrossRef]
  144. Abad, F.X.; Villena, C.; Guix, S.; Caballero, S.; Pinto, R.M.; Bosch, A. Potential role of fomites in the vehicular transmission of human astroviruses. Appl. Environ. Microbiol. 2001, 67, 3904–3907. [Google Scholar] [CrossRef] [PubMed]
  145. Kurtz, J.B.; Lee, T.W.; Parsons, A.J. The action of alcohols on rotavirus, astrovirus and enterovirus. J. Hosp. Infect. 1980, 1, 321–325. [Google Scholar] [CrossRef]
  146. Caballero, S.; Guix, S.; Ribes, E.; Bosch, A.; Pinto, R.M. Structural requirements of astrovirus virus-like particles assembled in insect cells. J. Virol. 2004, 78, 13285–13292. [Google Scholar] [CrossRef] [PubMed]
  147. Dalton, R.M.; Pastrana, E.P.; Sánchez-Fauquier, A. Vaccinia virus recombinant expressing an 87-kilodalton polyprotein that is sufficient to form astrovirus-like particles. J. Virol. 2003, 77, 9094–9098. [Google Scholar] [CrossRef] [PubMed]
  148. Xia, M.; Wei, C.; Wang, L.; Cao, D.; Meng, X.J.; Jiang, X.; Tan, M. A trivalent vaccine candidate against hepatitis e virus, norovirus, and astrovirus. Vaccine 2016, 34, 905–913. [Google Scholar] [CrossRef] [PubMed]
  149. Xia, M.; Wei, C.; Wang, L.; Cao, D.; Meng, X.J.; Jiang, X.; Tan, M. Development and evaluation of two subunit vaccine candidates containing antigens of hepatitis e virus, rotavirus, and astrovirus. Sci. Rep. 2016, 6, 25735. [Google Scholar] [CrossRef] [PubMed]
  150. Bjorkholm, M.; Celsing, F.; Runarsson, G.; Waldenstrom, J. Successful intravenous immunoglobulin therapy for severe and persistent astrovirus gastroenteritis after fludarabine treatment in a patient with Waldenström's macroglobulinemia. Int. J. Hematol. 1995, 62, 117–120. [Google Scholar] [CrossRef]
  151. Superti, F.; Seganti, L.; Orsi, N.; Desideri, N.; Stein, M.L.; Tinari, A.; Marziano, M.L.; Donelli, G. In vitro effect of synthetic flavanoids on astrovirus infection. Antivir. Res. 1990, 13, 201–208. [Google Scholar] [CrossRef]
  152. Tellez, M.A.; Tellez, A.N.; Velez, F.; Ulloa, J.C. In vitro antiviral activity against rotavirus and astrovirus infection exerted by substances obtained from Achyrocline bogotensis (Kunth) DC. (Compositae). BMC Complement. Altern. Med. 2015, 15, 428. [Google Scholar] [CrossRef] [PubMed]
Viruses 09 00033 g001 550
Figure 1. Phylogenetic tree of representative members of the Astroviridae family. The tree was constructed based on complete capsid amino acid sequences, using the Neighbor Joining method implemented in the MEGA6 program [27]. The tree is drawn to scale, with branch lengths in the same units as those of the evolutionary distances (p-distance) used to infer the phylogenetic tree. All positions containing alignment gaps and missing data were removed only in pairwise sequence comparisons (pairwise deletion option). Viruses infecting birds are shown in brown, while viruses infecting humans are shown in red.
Figure 1. Phylogenetic tree of representative members of the Astroviridae family. The tree was constructed based on complete capsid amino acid sequences, using the Neighbor Joining method implemented in the MEGA6 program [27]. The tree is drawn to scale, with branch lengths in the same units as those of the evolutionary distances (p-distance) used to infer the phylogenetic tree. All positions containing alignment gaps and missing data were removed only in pairwise sequence comparisons (pairwise deletion option). Viruses infecting birds are shown in brown, while viruses infecting humans are shown in red.
Viruses 09 00033 g001
Table
Table 1. Amino acid sequence identity between classic HAstVs, MLB-HAstVs (Human astrovirus Melbourne) and VA-HAstV (Human astrovirus Virginia), for the 3 open reading frames (ORFs). Representative members of each group were used for calculations (Classic: L23513, L13745, AF141381, AY720891, DQ028633, HM237363, Y08632, AF260508; MLB: FJ222451, JF742759, JX857870; VA2-VA4: GQ502193, JX857869; VA1-VA3: FJ973620, JX857868; VA5: KJ656124. The grouping of serotypes and clades into the different International Committee on Taxonomy of Viruses (ICTV) recognized species within the Mamastrovirus genus is indicated.
Table 1. Amino acid sequence identity between classic HAstVs, MLB-HAstVs (Human astrovirus Melbourne) and VA-HAstV (Human astrovirus Virginia), for the 3 open reading frames (ORFs). Representative members of each group were used for calculations (Classic: L23513, L13745, AF141381, AY720891, DQ028633, HM237363, Y08632, AF260508; MLB: FJ222451, JF742759, JX857870; VA2-VA4: GQ502193, JX857869; VA1-VA3: FJ973620, JX857868; VA5: KJ656124. The grouping of serotypes and clades into the different International Committee on Taxonomy of Viruses (ICTV) recognized species within the Mamastrovirus genus is indicated.
Mamastrovirus SpeciesClassicMLBVA2-VA4VA1-VA3VA5
Mamastrovirus 1Mamastrovirus 6Mamastrovirus 8Mamastrovirus 9Unassigned
Serotypes/CladesHAstV-1 to 8MLB1, MLB2 and MLB3VA2 (HMO-A) and VA4VA1 (HMO-C) and VA3 (HMO-B)VA5
ORF1a (protease and other nonstructural proteins)
Classic100––––
MLB32.8100–––
VA2-VA424.129.1100––
VA1-VA324.228.967.4100–
VA523.928.261.559.6100
ORF1b (RNA dependent RNA polymerase)
Classic100––––
MLB54.5100–––
VA2-VA451.849.4100––
VA1-VA353.049.373.7100–
VA550.250.774.071.5100
ORF2 (capsid proteins)
Classic100––––
MLB27.5100–––
VA2-VA424.021.9100––
VA1-VA323.022.151.9100–
VA523.820.658.953.1100
Table
Table 2. Summary of the 9 case reports of HAstV infections causing severe central nervous system (CNS) infections in humans (adapted from [50] and updated).
Table 2. Summary of the 9 case reports of HAstV infections causing severe central nervous system (CNS) infections in humans (adapted from [50] and updated).
Type of Novel HAstVYearCountryAge of PatientUnderlying ConditionType of CNS Infection/PresentationTreatmentIS/OtherOutcomeReference
Mamastrovirus 1
HAstV-42008Switzerland3 monthsHSCT for severe combined immunodeficiencyMeningoencephalitisNoneNot describedDead[41]
Mamastrovirus 6
MLB12015Japan4 yearsCB HSCT for congenital aplastic anemia
GvH disease		EncephalitisAciclovir
IVIG
Edaravone		Ciclosporin
MMF		Alive[53]
MLB22014Switzerland21 yearsHealthyAcute meningitisCeftriaxone AciclovirNoneAlive[52]
MLB22014Switzerland37 yearsHSCT for acute myeloid leukemia, relapseMeningitisNoneIT chemotherapy 5-AZC
Cranial irradiation		Dead[52]
Mamastrovirus 9
VA1 (HAstV-PS)2007US15 yearsX-linked agammaglobulinemiaHeadache, suicidal and homicidal ideation, memory loss, ataxia, progressive cognitive declineNoneRelated to underlying diseaseDead[47]
VA12013UK42 yearsHSCT for chronic lymphocytic leukemiaProgressive sensorineural deafness EncephalitisValaciclovir
BS antibiotics
Steroids
IVIG
Ribavirin		Not describedDead[49]
VA12014France14 yearsX-linked agammaglobulinemiaFour-year history of progressive cognitive impairment, ataxia and seizure.IVIG
Steroid
Ribavirin
PEG IFN alpha-2b		Related to underlying diseaseAlive[50]
VA12015UK18 monthsHSCT for cartilage hair hypoplasia
GvH disease		EncephalitisCidofovir *
Adenovirus-specific DLI *		Ciclosporin
MMF
Steroids		Dead[48]
VA12015UK8 monthsHSCT for acute myeloid leukemia
GvH grade 1		EncephalitisDLICiclosporin **Dead[51]
CB: Cord blood; HSCT: Hematopoietic stem cell transplantation; GvH: Graft-versus-host disease; IS: Immune suppression; MMF: Mycophenolate mofetil; 5-AZC: 5-azacitidine; BS: Broad spectrum; CNS: Central nervous system; CSF: Cerebrospinal fluid; HSCT: Human stem cell transplant; IT: Intrathecal; HAstV-PS: Human astrovirus Puget Sound; BMT: Bone marrow transplant; NP: Not performed; IVIG: Intravenous immunoglobulin; DLI: Donor lymphocytes infusion; * for adenovirus infection prior to CNS complication; ** tapered off at the time of CNS complication.
Table
Table 3. Major epidemiological studies to determine the classic HAstV positivity rate among different populations, published over the last 10 years.
Table 3. Major epidemiological studies to determine the classic HAstV positivity rate among different populations, published over the last 10 years.
Geographical Area (Time of Study)Type of IndividualsMethodPositivity Rate (%)% of Positive Samples Containing Other Pathogens (Type)Serotype PrevalencesReference
Children with symptoms of AGE
Asia
China (2007–2008)Outpatients < 15RT-PCR13.6N/AHAstV-1 (100%)[76]
China (2008–2009)Hospitalized < 5RT-PCR4.626 (other enteric viruses)HAstV-1 (100%)[77]
China (2010–2011)Outpatients < 5RT-PCR1.850 (other enteric viruses)HAstV-1 (100%)[78]
China (2010–2011)Outpatients < 5RT-PCR2.964 (rotavirus)HAstV-1 (100%)[68]
China (2005–2006)<5RTqPCR9.1N/AHAstV-1 (96%); HAstv-3 (4%)[79]
India (2004–2008)Hospitalized < 5RT-PCR3.18.8 (rotavirus)HAstV-1 (68%); HAstv-2 (10%); HAstV-8 (16%); HAstV-5 (6%)[80]
Japan (2009–2013)Outpatients < 5RT-PCR2.40N/A[81]
Japan (2009/10, 2014/15)<15RT-PCR4.2N/AHAstV-1 (54%); HAstv-4 (23%); HAstV-8 (16%); HAstV-6 (7%)[82]
Japan (2008/09, 2013/14)Hospitalized < 15 with suspected viral gastroenteritisRT-PCR1.6N/AHAstV-1 (81%); HAstV-8 (16%); HAstV-3 (3%)[83]
Japan (2012–2013)OutpatientsRT-PCR5.229 (other enteric viruses)HAstV-1 (76%); HAstv-4 (24%)[84]
Taiwan (2009–2011)Hospitalized < 5RT-PCR2.620 (other enteric viruses)N/A[85]
Thailand (2000–2003, 2005, 2007–2008, 2010–2011)Hospitalized < 5RT-PCR1.414 (rotavirus)HAstV-1 (58%); HAstv-3 (21%); HAstV-5 (14%); HAstV-3 (7%)[86]
Vietnam (2002–2003)Hospitalized < 9Multiplex RT-PCR0.633 (other enteric viruses)HAstV-1 (100%)[72]
Vietnam (2005–2006)Hospitalized and outpatients < 15RT-PCR13.928 (other enteric viruses)HAstV-1 (100%)[87]
Africa
Burkina Faso (November 2011–September 2012)Outpatients < 5RTqPCR4.97.7 (other enteric viruses)HAstV-1 (42%); HAstv-2 (25%); HAstV-8 (25%); HAstV-5 (8%)[88] *
Gabon (2010–2011)Outpatients < 5RT-PCR6.355 (other enteric viruses)HAstV-1 (89%); HAstv-4 (11%)[89]
Ghana (November 2005–January 2006)Outpatients < 5RT-PCR4.8N/AN/A[90] *
Kenya and Gambia (2008–2009)< 5RT-PCR2.7N/AN/A[20] *
Europe and Middle East
Bulgaria (summer 2009)Hospitalized < 3, summer monthsRT-PCR6.950 (other enteric viruses, bacteria and parasites)HAstV-1 (86%); HAstv-3 (14%)[91]
Finland (2009–2010)Children < 2 enrolled in prospective cohort INDIS StudyRTqPCR1.933 (other enteric viruses)N/A[92]
Italy (2008–2009)Hospitalized < 13RT-PCR2.10 (other enteric viruses)HAstV-1 (73%); HAstv-2 (20%); HAstV-4 (7%)[93]
Italy (2008–2009)Hospitalized < 18Multiplex RT-PCR00N/A[73]
Moldova and Ukraine (2009)Hospitalized < 5, negative for rotavirusRTqPCR1.414.3 (other enteric viruses)HAstV-1 (80%); HAstv-8 (20%)[94]
Qatar (June-November 2009)Outpatients < 20Multiplex RTqPCR0.7N/AN/A[74]
United Kingdom (2006–2007)Hospitalized < 16, health-care associated AGERT-PCR557 (other enteric viruses)N/A[71]
Central and South America
Brazil (1994–1996; 1995–1999)Outpatients < 6RT-PCR7.6; 29.722; 50 children with AGE and controls (other enteric viruses)HAstV-1 (58%); HAstV-2 (24%); HAstV-8 (12%); HAstV-3 (6%)[38] *
Brazil (1997–1999)Outpatients < 2RT-PCR1155 (other enteric viruses)HAstV-1 (92%); HAstV-2 (2%); HAstV-3 (2%); HAstV-4 (2%); HAstV-5 (2%)[95] *
Brazil (1994–1996; 1998–2002)Hospitalized < 5RT-PCR4.330.4 children with AGE and controls (other enteric viruses)N/A[96] *
Brazil (2005–2011)Children < 5, negative for rotavirus and norovirusRT-PCR7.1N/AHAstV-1 (70%); HAstV-2 (12%); HAstV-3 (10%); HAstV-8 (4%);
HAstV-4 (2%); HAstV-6 (2%)		[69]
Venezuela (2003)Outpatients < 5Multiplex RT-PCR1.529 (other enteric viruses)HAstV-1 (67%); HAstV-3 (33%)[75]
North America
US (2006–2009)Hospitalized and outpatientsRT-PCR3.1N/AN/A[8]
US (2008–2009)Hospitalized and outpatients < 5RTqPCR4.925 children with AGE and controls (other enteric viruses)HAstV-1 (52%); HAstV-2 (19%);
HAstV-4 (8%); HAstV-8 (3%)		[39] *
Children without diarrhea disorders
Burkina Faso (November 2011–September 2012)Matched controls < 5RTqPCR2N/AHAstV-1 (42%); HAstv-2 (25%); HAstV-8 (25%); HAstV-5 (8%)[88] *
Brazil (1997–1999)< 2RT-PCR320 (other enteric viruses)HAstV-1 (92%); HAstV-2 (2%); HAstV-3 (2%); HAstV-4 (2%); HAstV-5 (2%)[95] *
Brazil (1994–1996; 1995–1999)< 6RT-PCR20.7; 16.322; 50 children with AGE and controls (other enteric viruses)HAstV-1 (58%); HAstV-2 (24%); HAstV-8 (12%); HAstV-3 (6%)[38] *
Brazil (1994–1996; 1998–2002)< 5RT-PCR0.530.4 children with AGE and controls (other enteric viruses)N/A[96] *
Ghana (November 2005–January 2006)Matched controls < 5RT-PCR1.6N/AN/A[90] *
Kenya and Gambia (2008–2009)< 5RT-PCR2.4N/AN/A[20] *
US (2008–2009)Matched controls < 5RTqPCR3.025 children with AGE and controls (other enteric viruses)HAstV-3 (57%)[39] *
Adults with AGE
China (2005–2006)Collected from CDC’s surveillanceRTqPCR5.4N/AHAstV-1 (96%); HAstv-3 (4%)[79]
China (2007–2008)Visiting an outpatient
clinic and/or emergency room		RT-PCR1.830 (other enteric viruses)N/A[97]
France (2010–2011)Consulting a general
practitioner		RT-PCR6.950 (other enteric viruses)N/A[98]
Russia (2005–2007)HospitalizedRT-PCR2.2N/AN/A[99]
Singapore (October 2013–January 2014)HospitalizedRT-PCR2N/AN/A[100]
US (2006–2009)Hospitalized and outpatientsRT-PCR1.2N/AN/A[8]
Immunocompromised
Brazil (2003–2004)HIV-seropositive children with and without diarrheaRT-PCR0; 110N/A[7]
US (2006–2009)HospitalizedRT-PCR7.4N/AN/A[8]
AGE: Acute Gastroenteritis; RT-PCR: Reverse Transcription Polymerase Chain Reaction; RTqPCR: Reverse Transcription Quantitative Polymerase Chain Reaction; N/A: Not available. * Case-control study.
Table
Table 4. Major epidemiological studies to determine the MLB-HAstV and VA-HAstV positivity rate in stool samples.
Table 4. Major epidemiological studies to determine the MLB-HAstV and VA-HAstV positivity rate in stool samples.
Geographical Area (Time of Study)Type of IndividualsMethodMLB Positivity Rate (%)VA Positivity Rate (%)Reference
Children and adults with AGE
India (2005–2006)Community-based samples from a birth cohortRT-PCR2.10.7[12]
China (2004–2005)Hospitalized patientsRT-PCR0.20[116]
China (2010–2011)Outpatients < 5RT-PCR1.20.3[68]
Japan (2012–2013)Outpatient childrenRT-PCR10.60.6[84]
Nepal (2006–2008)Adults, negative for bacteria, rotavirus, adenovirus, HAstV, Giardia, Cryptosporidium or norovirus.RT-PCR02.1[14] *
Kenya and Gambia (2008–2009)Children < 5 from rural areasRT-PCR4.31.3[20] *
UK (2013–2014)Immunosuppressed and immunocompetent children and adultsRTqPCR (VA1)N/A0.3[48]
Egypt (2006–2007)Outpatients < 5RT-PCR1.40.5[117]
Turkey (2004–2005)Children < 5, negative for rotavirusRT-PCR0.70[118]
Brazil (2005–2011)Children < 2, negative for rotavirus and norovirusRT-PCR10[69]
US (2008)< 5RT-PCR0.60[13]
Children and adults without diarrhea disorders
Nepal (2006–2008)Adults, negative for bacteria, rotavirus, adenovirus, HAstV, Giardia, Cryptosporidium or norovirusRT-PCR01[14] *
Kenya and Gambia (2008–2009)Children < 5 from rural areasRT-PCR6.41.8[20] *
Children with non-polio acute flaccid paralysis (AFP)
Nigeria (2006–2008)Children < 15RT-PCR4.23.2[14]
Pakistan (2006–2008)Children < 15RT-PCR04.6[14]
Children and adults (undefined clinical presentation)
Switzerland (2014–2015)Children and adults stool specimens stored at a Laboratory of Virology of a University hospitalRTqPCR (MLB2)0.9N/A[52]
AGE: Acute Gastroenteritis; RT-PCR: Reverse Transcription Polymerase Chain Reaction; RTqPCR: Reverse Transcription Quantitative Polymerase Chain Reaction; N/A: Not available. * Case-control study.

Share and Cite

MDPI and ACS Style

Vu, D.-L.; Bosch, A.; Pintó, R.M.; Guix, S. Epidemiology of Classic and Novel Human Astrovirus: Gastroenteritis and Beyond. Viruses 2017, 9, 33. https://doi.org/10.3390/v9020033

AMA Style

Vu D-L, Bosch A, Pintó RM, Guix S. Epidemiology of Classic and Novel Human Astrovirus: Gastroenteritis and Beyond. Viruses. 2017; 9(2):33. https://doi.org/10.3390/v9020033

Chicago/Turabian Style

Vu, Diem-Lan, Albert Bosch, Rosa M. Pintó, and Susana Guix. 2017. "Epidemiology of Classic and Novel Human Astrovirus: Gastroenteritis and Beyond" Viruses 9, no. 2: 33. https://doi.org/10.3390/v9020033

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop