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. 2021 Sep 7;8(1):49.
doi: 10.1186/s40779-021-00340-5.

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

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

Duo-Meng Yang et al. Mil Med Res. .

Abstract

Retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5) sense viral RNA and activate antiviral immune responses. Herein we investigate their functions in human epithelial cells, the primary and initial target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A deficiency in MDA5, RIG-I or mitochondrial antiviral signaling protein (MAVS) enhanced viral replication. The expression of the type I/III interferon (IFN) during infection was impaired in MDA5-/- and MAVS-/-, but not in RIG-I-/-, when compared to wild type (WT) cells. The mRNA level of full-length angiotensin-converting enzyme 2 (ACE2), the cellular entry receptor for SARS-CoV-2, was ~ 2.5-fold higher in RIG-I-/- than WT cells. These data demonstrate MDA5 as the predominant SARS-CoV-2 sensor, IFN-independent induction of ACE2 and anti-SARS-CoV-2 role of RIG-I in epithelial cells.

Keywords: Melanoma differentiation-associated protein 5; Pathogen pattern recognition receptor; Retinoic acid-inducible gene I; SARS-CoV-2.

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Conflict of interest statement

The authors declare that they have no competing interests.

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