Journal
JOURNAL OF VIROLOGY
Volume 80, Issue 14, Pages 7245-7259Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.00463-06
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Funding
- NCI NIH HHS [CA77816, R01 CA077816, CA94079, R01 CA094079] Funding Source: Medline
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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.
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