Escape and Over-Activation of Innate Immune Responses by SARS-CoV-2: Two Faces of a Coin

In the past 20 years, coronaviruses (CoVs), including SARS-CoV-1, MERS-CoV, and SARS-CoV-2, have rapidly evolved and emerged in the human population. The innate immune system is the first line of defense against invading pathogens. Multiple host cellular receptors can trigger the innate immune system to eliminate invading pathogens. However, these CoVs have acquired strategies to evade innate immune responses by avoiding recognition by host sensors, leading to impaired interferon (IFN) production and antagonizing of the IFN signaling pathways. In contrast, the dysregulated induction of inflammasomes, leading to uncontrolled production of IL-1 family cytokines (IL-1β and IL-18) and pyroptosis, has been associated with COVID-19 pathogenesis. This review summarizes innate immune evasion strategies employed by SARS-CoV-1 and MERS-CoV in brief and SARS-CoV-2 in more detail. In addition, we outline potential mechanisms of inflammasome activation and evasion and their impact on disease prognosis.