The C-X-C chemokine IP-10 stimulates HIV-1 replication.
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.
Lane
Brian R
BR
Division of Infectious Diseases, Department of Internal Medicine, University of Michigan Medical Center, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0640, USA.
King
Steven R
SR
Bock
Paul J
PJ
Strieter
Robert M
RM
Coffey
Michael J
MJ
Markovitz
David M
DM
D002448:Cell Adhesion; D002478:Cells, Cultured; D017931:DNA Primers; D004279:DNA, Viral / Q000235:genetics; D015967:Gene Expression Regulation, Viral; D017930:Genes, Reporter; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000502:physiology / Q000821:virology; D008156:Luciferases / Q000235:genetics; D008214:Lymphocytes / Q000502:physiology / Q000821:virology; D016133:Polymerase Chain Reaction / Q000379:methods; D012194:RNA-Directed DNA Polymerase / Q000032:analysis; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D014779:Virus Replication / Q000502:physiology*
C515187:CXCR3 protein, human; D017931:DNA Primers; D004279:DNA, Viral; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D011994:Recombinant Proteins; D008156:Luciferases; D012194:RNA-Directed DNA Polymerase