| First Author | Neupane B | Year | 2020 |
| Journal | Front Immunol | Volume | 11 |
| Pages | 588382 | PubMed ID | 33304351 |
| Mgi Jnum | J:335604 | Mgi Id | MGI:6729317 |
| Doi | 10.3389/fimmu.2020.588382 | Citation | Neupane B, et al. (2020) Interleukin-17A Facilitates Chikungunya Virus Infection by Inhibiting IFN-alpha2 Expression. Front Immunol 11:588382 |
| abstractText | Interferons (IFNs) are the key components of innate immunity and are crucial for host defense against viral infections. Here, we report a novel role of interleukin-17A (IL-17A) in inhibiting IFN-alpha2 expression thus promoting chikungunya virus (CHIKV) infection. CHIKV infected IL-17A deficient (Il17a(-/-) ) mice expressed a higher level of IFN-alpha2 and developed diminished viremia and milder footpad swelling in comparison to wild-type (WT) control mice, which was also recapitulated in IL-17A receptor-deficient (Il17ra(-/-) ) mice. Interestingly, IL-17A selectively blocked IFN-alpha2 production during CHIKV, but not West Nile virus (WNV) or Zika virus (ZIKV), infections. Recombinant IL-17A treatment inhibited CHIKV-induced IFN-alpha2 expression and enhanced CHIKV replication in both human and mouse cells. We further found that IL-17A inhibited IFN-alpha2 production by modulating the expression of Interferon Regulatory Factor-5 (IRF-5), IRF-7, IFN-stimulated gene 49 (ISG-49), and Mx1 expression during CHIKV infection. Neutralization of IL-17A in vitro leads to the increase of the expression of these antiviral molecules and decrease of CHIKV replication. Collectively, these results suggest a novel function of IL-17A in inhibiting IFN-alpha2-mediated antiviral responses during CHIKV infection, which may have broad implications in viral infections and other inflammatory diseases. |
