title: Disruption of host antiviral resistances by gammaherpesvirus tegument proteins with homology to the FGARAT purine biosynthesis enzyme.
abstract: All known gammaherpesviruses encode at least one conserved tegument protein that contains sequence homology to the cellular purine biosynthesis enzyme: phosphoribosylformylglycineamide amidotransferase (FGARAT, or PFAS). While no enzymatic activity have been found on these viral FGARAT-homology proteins (vFGARAT), they are important for disarming host intrinsic antiviral machinery. Most vFGARAT proteins disrupt the intrinsic antiviral response-associated cellular subnuclear structure: ProMyelocytic Leukemia (PML) associated nuclear body (PML-NB). vFGARATs from different viruses target different components of PML-NB to prevent cellular repression of viral infection. In addition, vFGARATs of rhadinoviruses were recently found to oligomerize with the cellular FGARAT to deamidate RIG-I and repress inflammatory cytokine production. In this review we discuss the diverse mechanisms of antiviral response disruption by gammaherpesvirus vFGARATs and the significance of the enzyme homology domain.
authors.affiliation: The Wistar Institute, Philadelphia, PA 19104, United States; Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA 19104, United States.
authors.forename: Kevin
authors.initials: K
authors.lastname: Tsai
authors.affiliation: The Wistar Institute, Philadelphia, PA 19104, United States.
authors.forename: Troy E
authors.initials: TE
authors.lastname: Messick
authors.affiliation: The Wistar Institute, Philadelphia, PA 19104, United States. Electronic address: Lieberman@wistar.org.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Lieberman
mesh_terms: D018142:Gammaherpesvirinae / Q000276:immunology* / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion; D007113:Immunity, Innate; D051026:Phosphoribosylglycinamide Formyltransferase / Q000235:genetics; D015678:Viral Structural Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D015678:Viral Structural Proteins; D051026:Phosphoribosylglycinamide Formyltransferase