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Virus‐induced autophagic degradation of STAT 2 as a mechanism for interferon signaling blockade
Author(s) -
Avia Miguel,
Rojas José M,
Miorin Lisa,
Pascual Elena,
Van Rijn Piet A,
Martín Verónica,
GarcíaSastre Adolfo,
Sevilla Noemí
Publication year - 2019
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201948766
Subject(s) - blockade , stat , interferon , microbiology and biotechnology , autophagy , mechanism (biology) , signal transduction , degradation (telecommunications) , virus , jak stat signaling pathway , chemistry , biology , virology , receptor , biochemistry , apoptosis , tyrosine kinase , stat3 , computer science , telecommunications , philosophy , epistemology
The mammalian interferon ( IFN ) signaling pathway is a primary component of the innate antiviral response, and viral pathogens have evolved multiple mechanisms to antagonize this pathway and to facilitate infection. Bluetongue virus ( BTV ), an orbivirus of the Reoviridae family, is transmitted by midges to ruminants and causes a disease that produces important economic losses and restriction to animal trade and is of compulsory notification to the World Organization for Animal Health (OIE). Here, we show that BTV interferes with IFN ‐I and IFN ‐ II responses in two ways, by blocking STAT 1 phosphorylation and by degrading STAT 2. BTV ‐ NS 3 protein, which is involved in virion egress, interacts with STAT 2, and induces its degradation by an autophagy‐dependent mechanism. This STAT 2 degradative process requires the recruitment of an E3‐Ub‐ligase to NS 3 as well as NS 3 K63 polyubiquitination. Taken together, our study identifies a new mechanism by which a virus degrades STAT 2 for IFN signaling blockade, highlighting the diversity of mechanisms employed by viruses to subvert the IFN response.