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RNF115 plays dual roles in innate antiviral responses by catalyzing distinct ubiquitination of MAVS and MITA.

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Zhang ZD,Xiong TC,Yao SQ,Wei MC,Chen M,Lin D,Zhong B

doi

10.1038/s41467-020-19318-3

subject

Has Abstract

pub_date

2020-11-02 00:00:00

pages

5536

issue

1

issn

2041-1723

pii

10.1038/s41467-020-19318-3

journal_volume

11

pub_type

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