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SARS-CoV-2 ORF3c suppresses immune activation by inhibiting innate sensing

3/2/2023

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Context: any virus tries to reduce immune detection and response.
​Read beyond the headlines.

This article deals with SARS-CoV-2 and how it tries to reduce our immune response against itself.

Pathogens are detected via different pathogen recognition receptors (PRRs). For RNA viruses, RIG-1, MDA5 are two of those PRRs. 
​Source
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This preprint shows SARS-CoV-2 ORF3c reduces RIG-I- and MDA5-mediated immune activation and interacts with the signaling adaptor MAVS. The reduction is clear, but do keep in mind that this is a reduction, not absence of a response.
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Is this new? No, this immunosuppressive activity of ORF3c is conserved among members of the subgenus sarbecovirus, including SARS-CoV and coronaviruses isolated from bats. But it is important to know, and these functional assays will be important to understand any mutations that may be selected in this protein and its functional consequences.
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The authors also show that this protein is not essential for virus replication in vitro. Proteins in other viruses, such as Influenza A Virus protein PB1-F2242 and HCV protein NS3/4A, can also inhibit innate sensing by binding to MAVS;

Influenza Virus Protein PB1-F2 Inhibits the Induction of Type I Interferon by Binding to MAVS and Decreasing Mitochondrial Membrane Potential | Journal of Virology (asm.org)

Hepacivirus NS3/4A Proteases Interfere with MAVS Signaling in both Their Cognate Animal Hosts and Humans: Implications for Zoonotic Transmission | Journal of Virology (asm.org)

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    Professor Marc Veldhoen is an immunology expert and leads the MVeldhoen lab at the Instituto de Medicina Molecular (iMM) in Lisbon, Portugal.

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