NLRC5/MHC class I transactivator: A key target for immune escape by SARS-CoV-2

Antigen presentation to CD8+ T cells by MHC class I molecules is essential for host defense against viral infections. Various mechanisms have evolved in multiple viruses to escape immune surveillance and defense to support viral proliferation in host cells. Through in vitro SARS-CoV-2 infection studies and analysis of COVID-19 patient samples, we found that SARS-CoV-2 suppresses the induction of the MHC class I pathway by inhibiting the expression and function of NLRC5, a major transcriptional regulator of MHC class I genes. In this review, we discuss the molecular mechanisms for suppression of the MHC class I pathway and clinical implications for COVID-19. Cytotoxic T cells recognize and kill virus-infected cells through the interaction between TCR and viral antigen-loaded MHC class I complex (left). SARS-CoV-2 ORF6 suppresses the expression of MHC class I by inhibiting the nuclear importation of STAT1 and NLRC5, resulting in the immune evasion from cytotoxic T cells (right). image