Norovirus mechanisms of immune antagonism

- Norovirus infections fail to elicit long-lasting robust immunity.
- Noroviruses are shed for prolonged times, suggesting incomplete immune clearance.
- Noroviruses block the host secretory pathway which likely impedes immune responses.
- The norovirus virulence factor 1 (VF1) protein antagonizes cytokine induction.
- The norovirus minor structural protein VP2 suppresses antigen presentation.

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.