UBXN1 interferes with Rig-I-like receptor-mediated antiviral immune response by targeting MAVS.

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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Antiviral Agents, Cell Line, Tumor, DEAD-box RNA Helicases, HEK293 Cells, Humans, Immunity, Innate, Interferon Type I, Protein Binding, RNA Interference, RNA Viruses, RNA, Small Interfering, Signal Transduction
Cell Rep
Date: Apr. 25, 2013
Download Curated Data For This Publication
166002
Switch View:
  • Interactions 6