title: UBXN1 interferes with Rig-I-like receptor-mediated antiviral immune response by targeting MAVS.
abstract: RNA viruses are sensed by RIG-I-like receptors (RLRs), which signal through a mitochondria-associated adaptor molecule, MAVS, resulting in systemic antiviral immune responses. Although RLR signaling is essential for limiting RNA virus replication, it must be stringently controlled to prevent damage from inflammation. We demonstrate here that among all tested UBX-domain-containing protein family members, UBXN1 exhibits the strongest inhibitory effect on RNA-virus-induced type I interferon response. UBXN1 potently inhibits RLR- and MAVS-induced, but not TLR3-, TLR4-, or DNA-virus-induced innate immune responses. Depletion of UBXN1 enhances virus-induced innate immune responses, including those resulting from RNA viruses such as vesicular stomatitis, Sendai, West Nile, and dengue virus infection, repressing viral replication. Following viral infection, UBXN1 is induced, binds to MAVS, interferes with intracellular MAVS oligomerization, and disrupts the MAVS/TRAF3/TRAF6 signalosome. These findings underscore a critical role of UBXN1 in the modulation of a major antiviral signaling pathway.
authors.affiliation: Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Penghua
authors.initials: P
authors.lastname: Wang
authors.forename: Long
authors.initials: L
authors.lastname: Yang
authors.forename: Gong
authors.initials: G
authors.lastname: Cheng
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Zhengyun
authors.initials: Z
authors.lastname: Xu
authors.forename: Fuping
authors.initials: F
authors.lastname: You
authors.forename: Qiang
authors.initials: Q
authors.lastname: Sun
authors.forename: Rongtuan
authors.initials: R
authors.lastname: Lin
authors.forename: Erol
authors.initials: E
authors.lastname: Fikrig
authors.forename: Richard E
authors.initials: RE
authors.lastname: Sutton
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000998:Antiviral Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D007370:Interferon Type I / Q000494:pharmacology*; D011485:Protein Binding; D034622:RNA Interference; D012328:RNA Viruses / Q000276:immunology / Q000502:physiology; D034741:RNA, Small Interfering / Q000378:metabolism; D011971:Receptors, Immunologic; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000998:Antiviral Agents; D007370:Interferon Type I; C505371:MAVS protein, human; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic; C504037:UBXN1 protein, human; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases
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