Abstract
This study demonstrates that several CC-chemokines, including those that inhibit entry and replication of macrophage-tropic strains of HIV, increase the replication of T cell (T)-tropic strains in CD4(+) T cells. Enhancement of T-tropic HIV replication is observed at early stages of replication, requires signaling through inhibitory guanine nucleotide-binding regulatory (Gi) proteins, and is associated with increased cell surface colocalization of CD4 and the T-tropic HIV coreceptor CXCR4. These findings may further our understanding of the factors that influence the replication and spread of T-tropic strains of HIV in vivo and suggest that the use of cell signaling CC-chemokines as therapeutic agents for the purpose of limiting HIV replication in vivo should be approached with caution.
MeSH terms
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Anti-HIV Agents / pharmacology
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CD4 Antigens / physiology
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CD4-Positive T-Lymphocytes / drug effects*
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CD4-Positive T-Lymphocytes / virology*
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CD8-Positive T-Lymphocytes / drug effects
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CD8-Positive T-Lymphocytes / virology
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Chemokine CCL5 / analogs & derivatives
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Chemokine CCL5 / antagonists & inhibitors
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Chemokine CCL5 / pharmacology
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Chemokine CCL5 / physiology
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Chemokines, CC / pharmacology*
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Chemokines, CC / physiology
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GTP-Binding Proteins / physiology
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HIV Infections / virology
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HIV Seronegativity
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HIV-1 / drug effects*
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HIV-1 / physiology*
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Humans
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In Vitro Techniques
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Receptors, CXCR4 / physiology
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Signal Transduction
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Virus Replication / drug effects*
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Virus Replication / physiology
Substances
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Anti-HIV Agents
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CD4 Antigens
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Chemokine CCL5
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Chemokines, CC
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Receptors, CXCR4
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aminooxypentane-RANTES
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GTP-Binding Proteins