| Autor: |
Akhee Sabiha Jahan, Elise Biquand, Raquel Muñoz-Moreno, Agathe Le Quang, Chris Ka-Pun Mok, Ho Him Wong, Qi Wen Teo, Sophie A. Valkenburg, Alex W.H. Chin, Leo Lit Man Poon, Artejan te Velthuis, Adolfo García-Sastre, Caroline Demeret, Sumana Sanyal |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
Cell Reports, Vol 30, Iss 5, Pp 1570-1584.e6 (2020) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2020.01.015 |
| Popis: |
Summary: 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. : Jahan et al. describe the role of Otub1, a deubiquitylase that is induced during virus infection in an interferon-dependent manner to regulate optimal signaling via the RIG-I pathway. Influenza A virus NS1 is able to bind and degrade newly synthesized Otub1 as a means to evade the innate immune response. Keywords: deubiquitylases, RIG-I signaling, ubiquitylation, innate immune response, RNA virus, influenza A, viral subversion strategies |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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