Innate immune sensing of coronavirus and viral evasion strategies

By Yusuke Kasuga, Baohui Zhu, Kyoung-Jin Jang, Ji-Seung Yoo. 2021

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The innate immune system is the first line of the host defense program against pathogens and harmful substances. Antiviral innate immune responses can be triggered by multiple cellular receptors sensing viral components. The activated innate immune system produces interferons (IFNs) and cytokines that perform antiviral functions to eliminate invading viruses. Coronaviruses are single-stranded, positive-sense RNA viruses that have a broad range of animal hosts. Coronaviruses have evolved multiple means to evade host antiviral immune responses. Successful immune evasion by coronaviruses may enable the viruses to adapt to multiple species of host organisms. Coronavirus transmission from zoonotic hosts to humans has caused serious illnesses, such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease-2019 (COVID-19), resulting in global health and economic crises. In this review, we summarize the current knowledge of the mechanisms underlying host sensing of and innate immune responses against coronavirus invasion, as well as host immune evasion strategies of coronaviruses. Understanding how the innate immune system senses coronaviruses and how coronaviruses can escape detection could provide novel approaches to tackle infections. Coronaviruses, including SARS-CoV-2, constantly evolve to manipulate, obstruct and evade host immune responses. A team led by Ji-Seung Yoo, Hokkaido University, Sapporo, Japan, reviewed understanding of innate immune responses to coronaviruses and viral evasion strategies. Two major receptor families recognise RNA viruses upon infection, but how they respond to SARS-CoV-2 is unclear. One receptor, TLR7, plays a critical role in sensing coronavirus infections, and mutations in the TLR7 gene are associated with severe illness and mortality in young Covid-19 patients. Activating host TLR pathways may prove a useful therapeutic approach. Further in-depth investigations are needed into specific coronavirus proteins and viral mechanisms that suppress host immunity.

Subfields: Infectious Diseases, Modeling and Simulation