Current Biology
Volume 7, Issue 2, February 1997, Pages 112-121
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Research Paper
CD4-independent association between HIV-1 gp120 and CXCR4: functional chemokine receptors are expressed in human neurons

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Abstract

Background: Chemokines are a family of protiens that chemoattract and activate immune cells by interacting with specific receptors on the surface of their targets. We have shown previously that chemokine receptors including the interleukin-8 receptor B (CXCR2) and the Duffy blood group antigen are expressed on subsets of neurons in various regions of the adult central nervous system.

Results: Using a combination of immunohistochemical staining and receptor-binding studies, we show that hNT cells, which are differentiated human neurons derived from the cell line NTera 2, express functional chemokine receptors of the C–X–C and C–C types. These chemokine receptors include CXCR2, CXCR4, CCR1 and CCR5. We demonstrate high-affinity binding of both types of chemokines to hNT neurons and dose-dependent chemotactic responses to these chemokines in differentiated, but not undifferentiated, NTera 2 cells. In addition, we show that the envelope glycoprotein from the T-cell-tropic human immunodeficiency virus 1 (HIV-1) strain IIIB is a CD4-independent, dose-dependent inhibitor of the binding of stromal cell-derived factor 1 to its receptor, CXCR4.

Conclusions: These data support the recent findings that members of the chemokine receptor family, including CCR5 and LESTR/Fusin (CXCR4), function as coreceptors in combination with CD4 for HIV-1 invasion. This is the first report of functional expression of chemokine receptors on human neurons. Furthermore, our studies provide evidence for the direct, CD4-independent association of the viral envelope protein of the HIV-1 strain IIIB with the chemokine receptor CXCR4.

Cited by (0)

J Hesselgesser, M Halks-Miller, V DelVecchio and R Horuk, Departments of Immunology and Pharmacology, Berlex Biosciences, 15049 San Pablo Avenue, Richmond, California 94804, USA.

SC Peiper, Departments of Pathology and Medicine, Henry Vogt Cancer Research Institute, University of Louisville, James Graham Brown Cancer Center Louisville, Kentucky 40292, USA.

J Hoxie and DL Kolson, Departments of Medicine, Microbiology and Neurology, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA.

D Taub, Clinical Service Program, SAIC-Frederick, National Cancer Institute, Frederick, Maryland 21702, USA.

E-Mail address for J Hesselgesser (corresponding author): [email protected].