CCL2 Increases X4-tropic HIV-1 Entry into Resting CD4+ T Cells*
- Department of Pediatrics, Division of Infectious Diseases, University of California San Diego, La Jolla, California 92093-0672
- 1 To whom correspondence should be addressed: Dept. of Pediatrics, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0672. Tel.: 858-534-7055; Fax: 858-534-7411; E-mail: saspector{at}ucsd.edu.
Abstract
During human immunodeficiency virus type 1 (HIV-1) infection, there is a strong positive correlation between CCL2 levels and HIV viral load. To determine whether CCL2 alters HIV-1 infection of resting CD4+ T cells, we infected purified resting CD4+ T cells after incubation with CCL2. We show that CCL2 up-regulates CXCR4 on resting CD4+ T cells in a CCR2-dependent mechanism, and that this augmentation of CXCR4 expression by CCL2 increases the ability of these cells to be chemoattracted to CXCR4 using gp120 and renders them more permissive to X4-tropic HIV-1 infection. Thus, CCL2 has the capacity to render a large population of lymphocytes more susceptible to HIV-1 late in the course of infection.
Footnotes
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↵2 The abbreviations used are: HIV-1, human immunodeficiency virus type 1; HIV, human immunodeficiency virus; APC, allophycocyanin; CCL, chemokine (C-C motif) ligand; CCR2, chemokine (C-C motif) receptor 2; CXCL12, chemokine (CXC motif) ligand 12; CXCR4, chemokine (CXC motif) receptor 4; Erk, extracellular signal-regulated kinase; F-actin, filamentous actin; FITC, fluorescein isothiocyanate; HLA-DR, human leukocyte antigen-DR; IL-2 intereukin-2; LTR, long terminal repeat; MAPK, mitogen-activated protein kinase; PBMC, peripheral blood mononuclear cells; DPBS, Dulbecco's phosphate-buffered saline; PE, phycoerythrin; PHA, phytohemagglutinin; PTX, pertussis toxin; RPII, RNA polymerase II; TCR, T cell receptor.
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↵* This work was supported, in whole or in part, by National Institutes of Health Grant AI068632 (NIAID). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Received May 29, 2008.
- Revision received September 9, 2008.
- The American Society for Biochemistry and Molecular Biology, Inc.
