Inhibition of the Antigen-Presenting Ability of Dendritic Cells Bynon-Structural Protein 2 of Influenza A Virus

Influenza A viruses (IAV), including human IAV and avian IAV (H9N2 subtype), are responsible for recurring influenza outbreaks worldwide in a wide range of mammalian and avian species. Dendritic cells (DCs) are specialised antigen presenting cells. However, while DCs can take up IAV and transmit it to other cells. DCs do not effectively present IAV antigens. It remains unclear why. We found that IAV Non-structural protein 2 (NS2) inhibited the maturation and antigen-presenting ability of DCs. We next examined a potential involvement of microRNAs (miRNAs). Analyses of avian DCs stimulated with avian IAV identified 9 upregulated and 10 downregulated miRNAs. Curiously, however, NS2-transfection did not alter miRNA expression in DCs, 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. Funding Statement: This work was supported by the National Key Research and Development Program of China (2017YFD500706), the Jiangsu Excellent Youth Natural Science Foundation (BK20190077), the National Natural Science Foundation of China (No. 31702197, 31930109, and 31772777), the Fundamental Research Funds for the Central Universities (JCQY201906), the Fundamental Research Funds for the Central Universities (KJQN2018034) and A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD). Declaration of Interests: The authors of this editorial have no conflicts of interest to declare. The authors have no other relevant affiliations or financial involvement in any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Ethics Approval Statement: This study was approve by the Ethics Committee of Animal Experiments center of Nanjing Agricultural University. All animal studies were approved by the Institutional Animal Care and Use Committee of Nanjing Agricultural University (SYXK-2017-0007), and followed the National Institutes of Health guidelines for the performance of animal experiments.