Type I and III interferon responses in SARS-CoV-2 infection

Abstract

SARS-CoV-2: exploring virus-triggered immune system dysfunction Extensive studies into how SARS-CoV-2 manipulates the immune system and influences the activity of host proteins are needed to improve treatments for COVID-19. SARS-CoV-2 evades or blocks elements of the immune system, including the antiviral activity of type I and type III interferons (IFN). You-Me Kim and Eui-Cheol Shin at the Korea Advanced Institute of Science and Technology, Daejeon, South Korea, reviewed understanding of how SARS-CoV-2 inhibits IFN responses. In infected cells, SARS-CoV-2 proteins use diverse methods to inhibit host IFN pathways, but type I IFN responses are still triggered in non-infected immune cells. The researchers believe this may explain the delayed but exaggerated type I IFN responses that contribute to the hyper-inflammation seen in critically ill patients. They call for further investigations into IFN and inflammatory responses in SARS-CoV-2 infection. Coronavirus disease 2019 (COVID-19), the current pandemic disease, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Type I and III interferons (IFNs) are innate cytokines that are important in the first-line defense against viruses. Similar to many other viruses, SARS-CoV-2 has evolved mechanisms for evading the antiviral effects of type I and III IFNs at multiple levels, including the induction of IFN expression and cellular responses to IFNs. In this review, we describe the innate sensing mechanisms of SARS-CoV-2 and the mechanisms used by SARS-CoV-2 to evade type I and III IFN responses. We also discuss contradictory reports regarding impaired and robust type I IFN responses in patients with severe COVID-19. Finally, we discuss how delayed but exaggerated type I IFN responses can exacerbate inflammation and contribute to the severe progression of COVID-19.