title: Vaccinia virus activation of CCR5 invokes tyrosine phosphorylation signaling events that support virus replication.
abstract: Vaccinia virus, a poxvirus, produces structurally distinct forms of virions for which the immediate events following cell entry are ill-defined. We provide evidence that intracellular mature virus (IMV) enters both permissive and nonpermissive T-cell lines and that introduction of CCR5 into nonpermissive mouse fibroblasts or human primary T cells renders the cells permissive for vaccinia replication. Notably, T cells expressing CCR5 in which tyrosine 339 in the intracellular region is replaced by phenylalanine no longer support virus replication or virus-inducible activation of specific host cell signaling effectors IRS-2, Grb2, and Erk1/2. We show that following IMV entry into the cell, the intact but not the tyrosine-deficient CCR5 is rapidly internalized and colocalizes with virus. This colocalization precedes virus-inducible signaling and replication.
authors.affiliation: Toronto General Research Institute, 67 College Street, Rm. 424, Toronto, Ontario M5G 2M1, Canada.
authors.forename: Ramtin
authors.initials: R
authors.lastname: Rahbar
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Murooka
authors.forename: Anna A
authors.initials: AA
authors.lastname: Hinek
authors.forename: Carole L
authors.initials: CL
authors.lastname: Galligan
authors.forename: Antonella
authors.initials: A
authors.lastname: Sassano
authors.forename: Celeste
authors.initials: C
authors.lastname: Yu
authors.forename: Kishore
authors.initials: K
authors.lastname: Srivastava
authors.forename: Leonidas C
authors.initials: LC
authors.lastname: Platanias
authors.forename: Eleanor N
authors.initials: EN
authors.lastname: Fish
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D005347:Fibroblasts / Q000378:metabolism* / Q000821:virology; D051380:GRB2 Adaptor Protein / Q000378:metabolism; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D041681:NIH 3T3 Cells; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D017354:Point Mutation; D011499:Protein Processing, Post-Translational / Q000235:genetics; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism* / Q000821:virology; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism; D014615:Vaccinia / Q000235:genetics / Q000378:metabolism; D014616:Vaccinia virus / Q000502:physiology*; D014779:Virus Replication / Q000502:physiology*
chemical_list: D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; C495949:Grb2 protein, mouse; C526297:IRS2 protein, human; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; C526298:Irs2 protein, mouse; D010750:Phosphoproteins; D019713:Receptors, CCR5; D014443:Tyrosine; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3