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Review
. 2016 Feb:16:24-30.
doi: 10.1016/j.coviro.2015.11.005. Epub 2015 Dec 7.

Norovirus mechanisms of immune antagonism

Alexa N Roth  1 , Stephanie M Karst  2
Affiliations
Review

Norovirus mechanisms of immune antagonism

Alexa N Roth et al. Curr Opin Virol. 2016 Feb.

Abstract

Noroviruses are a leading cause of gastroenteritis outbreaks globally. Several lines of evidence indicate that noroviruses can antagonize or evade host immune responses, including the absence of long-lasting immunity elicited during a primary norovirus exposure and the ability of noroviruses to establish prolonged infections that are associated with protracted viral shedding. Specific norovirus proteins possessing immune antagonist activity have been described in recent years although mechanistic insight in most cases is limited. In this review, we discuss these emerging strategies used by noroviruses to subvert the immune response, including the actions of two nonstructural proteins (p48 and p22) to impair cellular protein trafficking and secretory pathways; the ability of the VF1 protein to inhibit cytokine induction; and the ability of the minor structural protein VP2 to regulate antigen presentation. We also discuss the current state of the understanding of host and viral factors regulating the establishment of persistent norovirus infections along the gastrointestinal tract. A more detailed understanding of immune antagonism by pathogenic viruses will inform prevention and treatment of disease.

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Figures

Figure 1
Figure 1. Norovirus proteins suppress antigen presentation and block cytokine induction, likely contributing to suboptimal memory immune responses and persistence establishment
Noroviruses encode multiple immunoregulatory functions. First, the norovirus VP2 protein prevents infected macrophages from upregulating molecules necessary for antigen presentation, including MHC class I, MHC class II, and costimulatory molecules CD40, CD80, and CD86. This activity regulates the induction of critical mediators of protective immunity including CD4+ T cells and antiviral antibody. Second, the norovirus VF1 protein blocks the induction of critical antiviral cytokines in infected cells, including type I IFN. This activity contributes to virulence and likely regulates the overall immune outcome to infection as well. Third, two norovirus nonstructural proteins, p48 and p22, inhibit host secretory pathways, a function that has been linked to immunoregulation for related virus families such as picornaviruses.
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References

    1. Ahmed SM, Hall AJ, Robinson AE, Verhoef L, Premkumar P, Parashar UD, Koopmans M, Lopman BA. Global prevalence of norovirus in cases of gastroenteritis: a systematic review and meta-analysis. Lancet Infect Dis. 2014;14:725–730. - PMC - PubMed
    1. Koo HL, Neill FH, Estes MK, Munoz FM, Cameron A, Dupont HL, Atmar RL. Noroviruses: The Most Common Pediatric Viral Enteric Pathogen at a Large University Hospital After Introduction of Rotavirus Vaccination. J Pediatr Infect Dis Soc. 2013;2:57–60. - PMC - PubMed
    1. Payne DC, Vinjé J, Szilagyi PG, Edwards KM, Staat MA, Weinberg GA, Hall CB, Chappell J, Bernstein DI, Curns AT, et al. Norovirus and Medically Attended Gastroenteritis in U.S. Children. N Engl J Med. 2013;368:1121–1130. - PMC - PubMed
    1. Koo HL, Ajami N, Atmar RL, DuPont HL. Noroviruses: The Principal Cause of Foodborne Disease Worldwide. Discov Med. 2010;10:61–70. - PMC - PubMed
    1. Kroneman A, Vega E, Vennema H, Vinjé J, White PA, Hansman G, Green K, Martella V, Katayama K, Koopmans M. Proposal for a unified norovirus nomenclature and genotyping. Arch Virol. 2013;158:2059–2068. - PMC - PubMed

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