Viral Mimicry of Interleukin-17A by SARS-CoV-2 ORF8
Xin Wu, Tian Xia, Woo-Jin Shin, Kwang-Min Yu, WooRam Jung, Alexandra Herrmann, Suan‐Sin Foo, Weiqiang Chen, Pengfei Zhang, Jong‐Soo Lee, Haryoung Poo, Suzy Comhair, Lara Jehi, Young Ki Choi, Armin Ensser, Jae U. Jung
Abstract
Patients infected with SARS-CoV-2 variants lacking open reading frame 8 (ORF8) have been associated with milder infection and disease outcome, but the molecular mechanism behind how this viral accessory protein mediates disease pathogenesis is not yet known. In our study, we revealed that secreted ORF8 protein mimics host IL-17 to activate IL-17 receptors A and C (IL-17RA/C) and induces a significantly stronger inflammatory response than host IL-17A, providing molecular insights into the role of ORF8 in COVID-19 pathogenesis and serving as a potential therapeutic target.