Abstract
Chemokines play critical roles in HIV-1 infection, serving both to modulate viral replication and to recruit target cells to sites of infection. Interferon-gamma-inducible protein 10 (IP-10/CXCL10) is a C-X-C chemokine that acts specifically upon activated T cells and macrophages and attracts T cells into the cerebrospinal fluid (CSF) in HIV-associated neurological disease. We now demonstrate that IP-10 stimulates HIV-1 replication in monocyte-derived macrophages and peripheral blood lymphocytes. We further demonstrate that neutralization of endogenous IP-10 or blocking the function of its receptor, CXCR3, reduces HIV-1 replication in these same cells. Therefore, blocking the interaction between IP-10 and CXCR3 represents a possible new target for anti-retroviral therapy.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Cell Adhesion
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Cells, Cultured
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DNA Primers
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DNA, Viral / genetics
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Gene Expression Regulation, Viral
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Genes, Reporter
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HIV Long Terminal Repeat
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HIV-1 / genetics
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HIV-1 / pathogenicity
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HIV-1 / physiology*
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Humans
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Leukocytes, Mononuclear / physiology
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Leukocytes, Mononuclear / virology
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Luciferases / genetics
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Lymphocytes / physiology
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Lymphocytes / virology
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Polymerase Chain Reaction / methods
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RNA-Directed DNA Polymerase / analysis
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Receptors, CXCR3
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Receptors, Chemokine / physiology*
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Recombinant Proteins / metabolism
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Transfection
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Virus Replication / physiology*
Substances
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CXCR3 protein, human
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DNA Primers
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DNA, Viral
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Receptors, CXCR3
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Receptors, Chemokine
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Recombinant Proteins
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Luciferases
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RNA-Directed DNA Polymerase