Interferon antagonists encoded by SARS-CoV-2 at a glance

Abstract

The innate immune system is a powerful barrier against invading pathogens. Interferons (IFNs) are a major part of the cytokine-mediated anti-viral innate immune response. After recognition of a pathogen by immune sensors, signaling cascades are activated that culminate in the release of IFNs. These activate cells in an autocrine or paracrine fashion eventually setting cells in an anti-viral state via upregulation of hundreds of interferon-stimulated genes (ISGs). To evade the anti-viral effect of the IFN system, successful viruses like the pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolved strategies to counteract both IFN induction and signaling. In fact, more than half of the about 30 proteins encoded by SARS-CoV-2 target the IFN system at multiple levels to escape IFN-mediated restriction. Here, we review recent insights into the molecular mechanisms used by SARS-CoV-2 proteins to suppress IFN production and the establishment of an anti-viral state.

The role of SARS-CoV-2 accessory proteins in immune evasion

“…Overall, it is clear that the accessory proteins play a critical role in inhibiting the activation of the IFN system. However, it seems that many of them perform other tasks in addition to hindering innate immunity, such as assisting in virion assembly and viral escape [58] .…”

The Host Response to Influenza A Virus Interferes with SARS-CoV-2 Replication during Coinfection

“…In addition, SARS-CoV-2 infection suppresses key components of the innate immune response. More than half of the 30 proteins encoded in the SARS-CoV-2 genome have been reported to counteract interferon (IFN) induction and signaling ( 12 ), raising concern about the risk for coinfection with other pathogens.…”

Pin-Pointing the Key Hubs in the IFN-γ Pathway Responding to SARS-CoV-2 Infection

“…SARS-CoV-2 has evolved several strategies to counteract not only IFN production but also IFN signaling. In fact, 16 viral proteins target the host’s IFN pathway at several levels to escape IFN-mediated restriction [ 15 ]. Although much attention has been placed on the SARS-CoV-2 mediated evasion of the IFN response, not much attention has been given to the role of IFN-γ-associated genes in COVID-19.…”