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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Amino Acid Substitution
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Animals
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Fibroblasts / metabolism*
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Fibroblasts / virology
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GRB2 Adaptor Protein / metabolism
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Humans
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Insulin Receptor Substrate Proteins
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Intracellular Signaling Peptides and Proteins
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Mice
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / metabolism
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NIH 3T3 Cells
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Phosphoproteins / metabolism
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Phosphorylation
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Point Mutation
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Protein Processing, Post-Translational / genetics
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Receptors, CCR5 / genetics
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Receptors, CCR5 / metabolism*
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Signal Transduction*
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T-Lymphocytes / metabolism*
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T-Lymphocytes / virology
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Tyrosine / genetics
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Tyrosine / metabolism
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Vaccinia / genetics
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Vaccinia / metabolism
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Vaccinia virus / physiology*
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Virus Replication / physiology*
Substances
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GRB2 Adaptor Protein
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GRB2 protein, human
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Grb2 protein, mouse
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IRS2 protein, human
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Insulin Receptor Substrate Proteins
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Intracellular Signaling Peptides and Proteins
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Irs2 protein, mouse
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Phosphoproteins
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Receptors, CCR5
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Tyrosine
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3