Control of Innate Immune Activation by Severe Acute Respiratory Syndrome Coronavirus 2 and Other Coronaviruses

J Interferon Cytokine Res. 2021 Jun;41(6):205-219. doi: 10.1089/jir.2021.0060.


The ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), represents a public health crisis of unprecedented proportions. After the emergence of SARS-CoV-1 in 2002, and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, this is the third outbreak of a highly pathogenic zoonotic coronavirus (CoV) that the world has witnessed in the last 2 decades. Infection with highly pathogenic human CoVs often results in a severe respiratory disease characterized by a delayed and blunted interferon (IFN) response, accompanied by an excessive production of proinflammatory cytokines. This indicates that CoVs developed effective mechanisms to overcome the host innate immune response and promote viral replication and pathogenesis. In this review, we describe the key innate immune signaling pathways that are activated during infection with SARS-CoV-2 and other well studied pathogenic CoVs. In addition, we summarize the main strategies that these viruses employ to modulate the host immune responses through the antagonism of IFN induction and effector pathways.

Keywords: SARS-CoV-2; coronavirus; immune evasion; innate immunity; interferon.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • COVID-19 / immunology*
  • COVID-19 / pathology*
  • Cricetinae
  • Cytokines / immunology
  • Genome, Viral / genetics
  • Humans
  • Immune Evasion / immunology*
  • Immunity, Innate / immunology*
  • Interferons / immunology
  • Mice
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / immunology*
  • Signal Transduction / immunology


  • Cytokines
  • Interferons