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Significance Virus-induced signal adaptor (VISA)/mitochondrial antiviral signaling protein (MAVS) is an essential adaptor protein in innate immune response to RNA viruses; understanding how VISA is regulated is important for the… Click to show full abstract
Significance Virus-induced signal adaptor (VISA)/mitochondrial antiviral signaling protein (MAVS) is an essential adaptor protein in innate immune response to RNA viruses; understanding how VISA is regulated is important for the treatment of infectious diseases. In this study, we discovered that tankyrase 1 (TNKS1) and TNKS2 negatively regulate innate antiviral response by catalyzing Poly(ADP-ribosyl)ation (PARylation) of VISA. This modification of VISA serves as a signal for the E3 ubiquitin ligase Ring figure protein 146 (RNF146), which polyubiquitinates VISA and leads to its degradation. Our findings reveal a mechanism for attenuating innate immune response to RNA viruses by the TNKS–RNF146 axis, which could help the development of drugs or vaccines against RNA virus infection.
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Year Published: 2022
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