Covid-19: Perspectives on Innate Immune Evasion

Abstract

The ongoing outbreak of Coronavirus disease 2019 infection achieved pandemic status on March 11, 2020. As of September 8, 2020 it has caused over 890,000 mortalities world-wide. Coronaviral infections are enabled by potent immunoevasory mechanisms that target multiple aspects of innate immunity, with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) able to induce a cytokine storm, impair interferon responses, and suppress antigen presentation on both MHC class I and class II. Understanding the immune responses to SARS-CoV-2 and its immunoevasion approaches will improve our understanding of pathogenesis, virus clearance, and contribute toward vaccine and immunotherepeutic design and evaluation. This review discusses the known host innate immune response and immune evasion mechanisms driving SARS-CoV-2 infection and pathophysiology.

Keywords: MHC trafficking; SARS-CoV-2; cytokine - immunological terms; innnate immune; macropahge.

FIGURE 1

CoV Innate Immune Evasion. The innate immune response to CoV’s is activated upon detection of viral pathogen-associated molecular patterns, such as double-stranded RNA, via host PRRs such as RIG-I. Following viral recognition, transcription factors including NF-κB, AP-1 and IRF3 are activated and translocate to the nucleus where they induce the expression of interferons. Both MERS-CoV and SARS-CoV, through their M, N, non-structural proteins (NSP1, 3b, 4a, 4b, 5, 6), and PLpro, have developed mechanisms to interfere with these signaling pathways. This alters the cytokine secretion profile of infected cells to enhance the recruitment of myeloid immune cells over NK cells, which in turn produce more cytokines, creating a cycle of inflammation that damages the lung. Many of these processes are likely conserved in SARS-CoV-2.