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

Abstract

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.

COVID-19 pandemic: A multidisciplinary perspective on the pathogenesis of a novel coronavirus from infection, immunity and pathological responses

“…Several mechanisms may exist for apoptosis, decreased expression, and functional failure of immune cells. The decrease in T-cell numbers was negatively correlated with IL-6 and TNF-a levels (164), suggesting that increased inflammatory cytokines may promote T-cell failure and apoptosis. Moreover, the IL-2 signaling pathway is inhibited, negatively regulating CD8 + T cells (71) and inducing a decrease in lymphocytes.…”

COVID-19 and the Immune Response: A Multi-Phasic Approach to the Treatment of COVID-19

“…SARS-CoV-2 has strategies to avoid being detected or acted upon by the immune system. Several studies have together shown that the SARS-CoV-2 immune evasion strategy involves restricting the interferon (IFN) system, resulting in low type I and II IFN responses, as well as low IFN-stimulated genes (ISGs) during the early stages of COVID-19 [ 31 , 32 ]. The SARS-CoV-2 proteins responsible for this include non-structural protein 1 (NSP1), NSP8, NSP9, NSP13, NSP15, ORF9b, and ORF6 [ 33 , 34 , 35 ].…”

Discovery of host-directed modulators of virus infection by probing the SARS-CoV-2-host protein-protein interaction network

“…In response to infection, host cells mount antiviral responses. However, SARS-CoV-2, like many other viruses, has developed various strategies to escape cellular antiviral responses, similarly to Dengue, SARS-CoV-1, MERS-CoV (1). It is therefore important to elucidate the interactions of the SARS-CoV-2 with host proteins to gain better insights into virus infection and pathogenesis, and to potentially reveal novel options for therapeutic intervention.…”