Inhibition of the antigen-presenting ability of dendritic cells by non-structural protein 2 of influenza A virus

Abstract

Influenza A viruses (IAV), including human IAV and avian IAV (H9N2 subtype), are recurring of influenza outbreaks worldwide in a wide range of mammalian and avian species. Dendritic cells (DCs) are specialised antigen presenting cells. Although DCs can take up IAV and transmit it to other cells, it still unclear why DCs do not effectively present IAV antigens. In this study, we found that Non-structural protein 2 (NS2) of IAV inhibited the maturation and antigen-presenting ability of DCs. We then examined a potential involvement of microRNAs (miRNAs). Analyses of avian DCs stimulated with avian IAV identified 9 upregulated and 10 downregulated miRNAs. However, nearly none microRNA has been significantly altered by NS2 stimulation. Moreover, we found that NS2 binds to exportin 5 (Xpo5), which inhibited miRNA biogenesis. Thus, hijacking of the miRNA biogenesis pathway appears to be one mechanism by which NS2 impairs antigen presentation. Furthermore, we found that NS2 directly interacts with interferon regulatory factor 3, which also inhibits the antigen-presenting ability of DCs. These results thus indicate that NS2-mediated impairment of antigen presentation by DCs might be a mechanism that contributes to the prevalence of the influenza virus.