1. RNF115 plays dual roles in innate antiviral responses by catalyzing distinct ubiquitination of MAVS and MITA.
- Author
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Zhang ZD, Xiong TC, Yao SQ, Wei MC, Chen M, Lin D, and Zhong B
- Subjects
- Animals, Cardiovirus Infections pathology, Cardiovirus Infections virology, Disease Models, Animal, Encephalomyocarditis virus immunology, Female, HEK293 Cells, Herpes Simplex pathology, Herpes Simplex virology, Herpesvirus 1, Human immunology, Host-Pathogen Interactions immunology, Humans, Lysine metabolism, Macrophages immunology, Macrophages virology, Male, Mice, Mice, Knockout, Primary Cell Culture, Protein Aggregates immunology, RNA, Small Interfering metabolism, Ubiquitin-Protein Ligases genetics, Ubiquitin-Protein Ligases physiology, Ubiquitination immunology, Adaptor Proteins, Signal Transducing metabolism, Cardiovirus Infections immunology, Herpes Simplex immunology, Immunity, Innate, Membrane Proteins metabolism, Ubiquitin-Protein Ligases metabolism
- Abstract
MAVS and MITA are essential adaptor proteins mediating innate antiviral immune responses against RNA and DNA viruses, respectively. Here we show that RNF115 plays dual roles in response to RNA or DNA virus infections by catalyzing distinct types of ubiquitination of MAVS and MITA at different phases of viral infection. RNF115 constitutively interacts with and induces K48-linked ubiquitination and proteasomal degradation of homeostatic MAVS in uninfected cells, whereas associates with and catalyzes K63-linked ubiquitination of MITA after HSV-1 infection. Consistently, the protein levels of MAVS are substantially increased in Rnf115
-/- organs or cells without viral infection, and HSV-1-induced aggregation of MITA is impaired in Rnf115-/- cells compared to the wild-type counterparts. Consequently, the Rnf115-/- mice exhibit hypo- and hyper-sensitivity to EMCV and HSV-1 infection, respectively. These findings highlight dual regulation of cellular antiviral responses by RNF115-mediated ubiquitination of MAVS and MITA and contribute to our understanding of innate immune signaling.- Published
- 2020
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