title: An important role for mitochondrial antiviral signaling protein in the Kaposi's sarcoma-associated herpesvirus life cycle.
abstract: Kaposi's sarcoma-associated herpesvirus (KSHV) has been shown to be recognized by two families of pattern recognition receptors (PRRs), Toll-like receptors (TLRs) and NOD-like receptors (NLRs). Here we show that MAVS and RIG-I (retinoic acid-inducible gene 1), an RLR family member, also have a role in suppressing KSHV replication and production. In the context of primary infection, we show that in cells with depleted levels of MAVS or RIG-I, KSHV transcription is increased, while beta interferon (IFN-β) induction is attenuated. We also observed that MAVS and RIG-I are critical during the process of reactivation. Depletion of MAVS and RIG-I prior to reactivation led to increased viral load and production of infectious virus. Finally, MAVS depletion in latent KSHV-infected B cells leads to increased viral gene transcription. Overall, this study suggests a role for MAVS and RIG-I signaling during different stages of the KSHV life cycle.
  
  
  OBJECTIVE
  We show that RIG-I and its adaptor protein, MAVS, can sense KSHV infection and that these proteins can suppress KSHV replication following primary infection and/or viral reactivation.
authors.affiliation: Lineberger Comprehensive Cancer Center, Program in Global Oncology, and Department of Microbiology & Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: West
authors.forename: Megan
authors.initials: M
authors.lastname: Wicks
authors.forename: Sean M
authors.initials: SM
authors.lastname: Gregory
authors.forename: Pauline
authors.initials: P
authors.lastname: Chugh
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Jacobs
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhang
authors.forename: Kurtis M
authors.initials: KM
authors.lastname: Host
authors.forename: Dirk P
authors.initials: DP
authors.lastname: Dittmer
authors.forename: Blossom
authors.initials: B
authors.lastname: Damania
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D002460:Cell Line; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D019288:Herpesvirus 8, Human / Q000276:immunology* / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D011971:Receptors, Immunologic; D015398:Signal Transduction; D014775:Virus Activation; D014779:Virus Replication
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C505371:MAVS protein, human; D011971:Receptors, Immunologic; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases