The MHC class I-mediated antigen presentation pathway plays a critical role in antiviral immunity. Here we show that the MHC class I pathway is targeted by SARS-CoV-2. Analysis of the gene expression profile from COVID-19 patients as well as SARS-CoV-2 infected epithelial cell lines reveals that the induction of the MHC class I pathway is inhibited by SARS-CoV-2 infection. We show that NLRC5, an MHC class I transactivator, is suppressed both transcriptionally and functionally by the SARS-CoV-2 ORF6 protein, providing a mechanistic link. SARS-CoV-2 ORF6 hampers type II interferon-mediated STAT1 signaling, resulting in diminished upregulation of NLRC5 and IRF1 gene expression. Moreover, SARS-CoV-2 ORF6 inhibits NLRC5 function via blocking karyopherin complex-dependent nuclear import of NLRC5. Collectively, our study uncovers an immune evasion mechanism of SARS-CoV-2 that targets the function of key MHC class I transcriptional regulators, STAT1-IRF1-NLRC5. The presentation of viral antigens to T cells via the MHC molecules is a critical component of the host response to viral infection. Here the authors suggest SARS-CoV-2 possesses the immune evasion strategy against the MHC class I pathway by targeting key transcriptional regulators.
【저자키워드】 viral infection, MHC class I, 【초록키워드】 SARS-CoV-2, viral infection, Gene Expression, T cells, SARS-COV-2 infection, host response, Protein, immune evasion, T cell, Viral, pathway, target, MHC class I, ORF6, Antigen presentation, Stat1, antiviral immunity, Critical, IRF1, mechanism, COVID-19 patients, Signaling, COVID-19 patient, epithelial cell, Viral antigen, viral antigens, upregulation, gene expression profile, type II interferon, NLRC5, transcriptional regulators, nuclear, MHC class, MHC molecules, resulting, inhibit, inhibited, suppressed, reveal, epithelial cell line, MHC molecule, the SARS-CoV-2, transcriptionally, 【제목키워드】 SARS-CoV-2, pathway, inhibit,