Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Jan;48(1):168-77.
doi: 10.1128/JCM.01622-09. Epub 2009 Oct 28.

Molecular epidemiology of genogroup II-genotype 4 noroviruses in the United States between 1994 and 2006

Du-Ping Zheng  1 , Marc-Alain Widdowson, Roger I Glass, Jan Vinjé
Affiliations

Molecular epidemiology of genogroup II-genotype 4 noroviruses in the United States between 1994 and 2006

Du-Ping Zheng et al. J Clin Microbiol. 2010 Jan.

Abstract

Human noroviruses (NoVs) of genogroup II, genotype 4 (GII.4) are the most common strains detected in outbreaks of acute gastroenteritis worldwide. To gain insight into the epidemiology and genetic variation of GII.4 strains, we analyzed 773 NoV outbreaks reported to the CDC from 1994 to 2006. Of these NoV outbreaks, 629 (81.4%) were caused by GII viruses and 342 (44.2%) were caused by GII.4 strains. The proportion of GII.4 outbreaks increased from 5% in 1994 to 85% in 2006, but distinct annual differences were noted, including sharp increases in 1996, 2003, and 2006 each associated with newly emerging GII.4 strains. Sequence analysis of the full-length VP1 gene of GII.4 strains identified in this study and from GenBank segregated these viruses into at least 9 distinct subclusters which had 1.3 to 3.2% amino acid variation between strains in different subclusters. We propose that GII.4 subclusters be defined as having >5% sequence variation between strains. Our data confirm other studies on the rapid emergence and displacement of highly virulent GII.4 strains.

PubMed Disclaimer

Figures

FIG. 1.
FIG. 1.
Distribution of NoV outbreaks reported to the CDC between 1994 and 2006. (Top) Outbreaks (n = 773) were grouped by year and divided into “all NoV outbreaks,” “GI,” “GII.4,” and “other GII.” The solid black line connects the percentages of GII.4 outbreaks for the years shown. (Bottom) The horizontal lines refer to the years that the different GII.4 subclusters were detected. Lines with an arrowhead indicate that viruses belonging to that GII.4 subcluster have been circulating beyond 2006. The name chosen for each subcluster refers to the earliest strain detected in the United States, and the number (in parentheses) refers to how many sequence variants have been detected.
FIG. 2.
FIG. 2.
Epidemiologic characteristics of 773 NoV outbreaks in the United States between 1994 and 2006. Distribution by genogroup and genetic cluster (A) and by setting of GII.4 outbreaks (n = 342) (B), GI outbreaks (n = 128) (C), and other GII outbreaks (n = 287) (D).
FIG. 3.
FIG. 3.
Seasonal distribution of NoV outbreaks by month (all [n = 708], GI [n = 119], other GII [n = 299], and GII.4 [n = 290]) reported to the CDC from 1994 to 2006. The months are indicated by the numbers 1 to 12 below the graph (e.g., 1 for January, 2 for February, etc.).
FIG. 4.
FIG. 4.
Dynamic activities of GII.4 sequence variants in the United States from 1994 to 2006. Each of the GII.4 sequence variants (n = 198) was plotted against the number of outbreaks (A), number of states (B), and years (C). Each vertical line on the x axis represents one sequence variant. The numbers 15 and 72 refer to sequence variants 15 and 72 on the x axis.
FIG. 5.
FIG. 5.
Genetic diversity of GII.4 sequence variants causing outbreaks in the United States from 1994 to 2006. An unrooted tree was generated on the basis of 198 unique GII.4 sequence variants (of a 277-nt region of VP1). Each of the subclusters was assigned a name of the representative strain that was first detected and selected for complete VP1 sequencing (underlined). The number of sequence variants is listed in parentheses; the years the viruses circulated and the states where the strains were detected are also given. The scale bar labeled 0.01 indicates the average distance by nucleotide differences (as a percentage). The states are indicated by the two-letter state codes as follows: Alabama (AL), Alaska (AK), Arkansas (AR), Arizona (AZ), California (CA), Colorado (CO), Connecticut (CT), Delaware (DE), Florida (FL), Georgia (GA), Illinois (IL), Indiana (IN), Kentucky (KY), Louisiana (LA), Idaho (ID), Massachusetts (MA), Maryland (MD), Maine (ME), Missouri (MO), Michigan (MI), Minnesota (MN), Montana (MT), North Carolina (NC), New Hampshire (NH), Nevada (NV), New Mexico (NM), New York (NY), Ohio (OH), Oregon (OR), Pennsylvania (PA), Rhode Island (RI), South Carolina (SC), Texas (TX), Tennessee (TN), Utah (UT), Virginia (VA), Washington (WA), Washington DC (DC), Wisconsin (WI), West Virginia (WV), Wyoming (WY). CS, cruise ship.
FIG. 6.
FIG. 6.
Phylogenetic relationships of GII.4 strains and proposed GII.4 subcluster nomenclature. The phylogenetic tree was based on 84 full-length VP1 amino acid sequences, including 11 representative sequences (underlined) characterized in this study and 73 sequences from GenBank. Subclusters are named after the first strain for which the VP1 sequence was publicly available in GenBank. The time span (in years) that strains in each subcluster circulated is listed. Sequence name was formatted as follows: GenBank accession number/strain name/year/country. Countries are shown as three-letter country codes as follows: Australia (AUS), China (CHN), Canada (CAN), Germany (DEU), France (FRA), Great Britain (GBR), Ireland (IRE), Japan (JPN), The Netherlands (NLD), Sweden (SWE), Spain (ESP), and the United States (USA).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Allen, D. J., J. J. Gray, C. I. Gallimore, J. Xerry, and M. Iturriza-Gomara. 2008. Analysis of amino acid variation in the P2 domain of the GII-4 norovirus VP1 protein reveals putative variant-specific epitopes. PLoS One 3:e1485. - PMC - PubMed
    1. Ando, T., S. S. Monroe, J. R. Gentsch, Q. Jin, D. C. Lewis, and R. I. Glass. 1995. Detection and differentiation of antigenically distinct small round-structured viruses (Norwalk-like viruses) by reverse transcription-PCR and Southern hybridization. J. Clin. Microbiol. 33:64-71. - PMC - PubMed
    1. Ando, T., M. N. Mulders, D. C. Lewis, M. K. Estes, S. S. Monroe, and R. I. Glass. 1994. Comparison of the polymerase region of small round structured virus strains previously classified in three antigenic types by solid-phase immune electron microscopy. Arch. Virol. 135:217-226. - PubMed
    1. Blanton, L. H., S. M. Adams, R. S. Beard, G. Wei, S. N. Bulens, M. A. Widdowson, R. I. Glass, and S. S. Monroe. 2006. Molecular and epidemiologic trends of caliciviruses associated with outbreaks of acute gastroenteritis in the United States, 2000-2004. J. Infect. Dis. 193:413-421. - PubMed
    1. Bull, R. A., E. T. Tu, C. J. McIver, W. D. Rawlinson, and P. A. White. 2006. Emergence of a new norovirus genotype II.4 variant associated with global outbreaks of gastroenteritis. J. Clin. Microbiol. 44:327-333. - PMC - PubMed

Substances