title: NV Proteins of Fish Novirhabdovirus Recruit Cellular PPM1Bb Protein Phosphatase and Antagonize RIG-I-Mediated IFN Induction.
abstract: Non virion (NV) protein expression is critical for fish Novirhabdovirus, viral hemorrhagic septicemia virus (VHSV) and infectious hematopoietic necrosis virus (IHNV), in vivo pathogenesis. However, the mechanism by which NV promotes the viral replication is still unclear. We developed an approach based on reverse genetics and interactomic and identified several NV-associated cellular partners underlying cellular pathways as potential viral targets. Among these cell partners, we showed that NV proteins specifically interact with a protein phosphatase, Mg2+/Mn2+-dependent, 1Bb (PPM1Bb) and recruit it in the close vicinity of mitochondria, a subcellular compartment important for retinoic acid-inducible gene-I- (RIG-I)-mediated interferon induction pathway. PPM1B proteins belong to the PP2C family of serine/threonine (Ser/Thr) protein phosphatase and have recently been shown to negatively regulate the host antiviral response via dephosphorylating Traf family member-associated NF-κB activator (TANK)-binding kinase 1 (TBK1). We demonstrated that NV proteins and PPM1Bb counteract RIG-I- and TBK1-dependent interferon (IFN) and IFN-stimulated gene promoter induction in fish cells and, hence, the establishment of an antiviral state. Furthermore, the expression of VHSV NV strongly reduced TBK1 phosphorylation and thus its activation. Our findings provide evidence for a previously undescribed mechanism by which a viral protein recruits PPM1Bb protein phosphatase to subvert innate immune recognition.
authors.affiliation: VIM, INRA, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Biacchesi
authors.affiliation: VIM, INRA, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Mérour
authors.affiliation: PAPPSO, Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Chevret
authors.affiliation: VIM, INRA, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
authors.forename: Annie
authors.initials: A
authors.lastname: Lamoureux
authors.affiliation: VIM, INRA, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Bernard
authors.affiliation: VIM, INRA, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Brémont
mesh_terms: D000818:Animals; D002460:Cell Line; D005393:Fish Diseases / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D029941:Fish Proteins / Q000378:metabolism*; D007372:Interferons / Q000378:metabolism*; D029141:Novirhabdovirus / Q000235:genetics / Q000378:metabolism*; D017686:Oncorhynchus mykiss / Q000378:metabolism* / Q000821:virology; D000071636:Protein Phosphatase 2C / Q000378:metabolism*; D018353:Rhabdoviridae Infections / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029941:Fish Proteins; D014764:Viral Proteins; D007372:Interferons; D000071636:Protein Phosphatase 2C