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. Supplementary Information The online version contains supplementary material available at 10.1186/s40779-021-00340-5.
【저자키워드】 SARS-CoV-2, retinoic acid-inducible gene I, Pathogen pattern recognition receptor, Melanoma differentiation-associated protein 5, 【초록키워드】 ACE2, coronavirus, Infection, interferon, anti-SARS-CoV-2, angiotensin-converting enzyme 2, Protein, cells, MDA5, viral replication, Melanoma, IFN, RIG-I, epithelial cells, Viral RNA, expression, wild type, function, MAVS, mitochondrial, deficiency, acute respiratory syndrome, supplementary material, human epithelial cells, antiviral signaling, full-length, mRNA level, antiviral immune responses, cellular entry receptor, initial, activate, predominant, was impaired, WT cells, 【제목키워드】 SARS-COV-2 infection, RIG-I, receptor,