Differential roles of RIG-I-like receptors in SARS-CoV-2 infection

Yang, D.; Geng, T.; Harrison, A. G.; WANG, P.

doi:10.1101/2021.02.10.430677

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bioRxiv · 10.1101/2021.02.10.430677

Differential roles of RIG-I-like receptors in SARS-CoV-2 infection

Yang, D.·Geng, T.·Harrison, A. G.·WANG, P.

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Abstract

The retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5) are the major viral RNA sensors that are essential for activation of antiviral immune responses. However, their roles in severe acute respiratory syndrome (SARS)-causing coronavirus (CoV) infection are largely unknown. Herein we investigate their functions in human epithelial cells, the primary and initial target of SARS-CoV-2, and the first line of host defense. A deficiency in MDA5 (MDA5-/-), RIG-I or mitochondrial antiviral signaling protein (MAVS) greatly enhanced viral replication. Expression of the type I/III interferons (IFN) was upregulated following infection in wild-type cells, while this upregulation was severely abolished in MDA5-/- and MAVS-/-, but not in RIG-I-/- cells. Of note, ACE2 expression was ~2.5 fold higher in RIG-I-/- than WT cells. These data demonstrate a dominant role of MDA5 in activating the type I/III IFN response to SARS-CoV-2, and an IFN-independent anti-SARS-CoV-2 role of RIG-I.

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Yang, D., Geng, T., Harrison, A. G., WANG, P.. 2021-02-11. Differential roles of RIG-I-like receptors in SARS-CoV-2 infection. https://doi.org/10.1101/2021.02.10.430677

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