Abstract：
:Deubiquitylases (DUBs) regulate critical signaling pathways at the intersection of host immunity and viral pathogenesis. Although RIG-I activation is heavily dependent on ubiquitylation, systematic analyses of DUBs that regulate this pathway have not been performed. Using a ubiquitin C-terminal electrophile, we profile DUBs that function during influenza A virus (IAV) infection and isolate OTUB1 as a key regulator of RIG-I-dependent antiviral responses. Upon infection, OTUB1 relocalizes from the nucleus to mitochondrial membranes together with RIG-I, viral PB2, and NS1. Its expression depends on competing effects of interferon stimulation and IAV-triggered degradation. OTUB1 activates RIG-I via a dual mechanism of K48 polyubiquitin hydrolysis and formation of an E2-repressive complex with UBCH5c. We reconstitute this mechanism in a cell-free system comprising [35S]IRF3, purified RIG-I, mitochondrial membranes, and cytosol expressing OTUB1 variants. A range of IAV NS1 proteins trigger proteasomal degradation of OTUB1, antagonizing the RIG-I signaling cascade and antiviral responses.
journal_name
Cell Repjournal_title
Cell reportsauthors
Jahan AS,Biquand E,Muñoz-Moreno R,Le Quang A,Mok CK,Wong HH,Teo QW,Valkenburg SA,Chin AWH,Man Poon LL,Te Velthuis A,García-Sastre A,Demeret C,Sanyal Sdoi
10.1016/j.celrep.2020.01.015subject
Has Abstractpub_date
2020-02-04 00:00:00pages
1570-1584.e6issue
5issn
2211-1247pii
S2211-1247(20)30024-3journal_volume
30pub_type
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