CD4-independent association between HIV-1 gp120 and CXCR4: functional chemokine receptors are expressed in human neurons.
Publication/Presentation Date
2-1-1997
Abstract
BACKGROUND: Chemokines are a family of proteins 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 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 NTera2, express functional chemokine receptors of the C-X-X 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 no t undifferentiated, NTera 2 cells. In addition, we show that the envelop 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 recent findings that members of the chemokine 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 for direct CD4-independent association of the viral envelope protein of the HIV-1 strain III with the chemokine receptor CXCR4.
Volume
7
Issue
2
First Page
112
Last Page
121
ISSN
0960-9822
Published In/Presented At
Hesselgesser, J., Halks-Miller, M., DelVecchio, V., Peiper, S. C., Hoxie, J., Kolson, D. L., Taub, D., & Horuk, R. (1997). CD4-independent association between HIV-1 gp120 and CXCR4: functional chemokine receptors are expressed in human neurons. Current biology : CB, 7(2), 112–121. https://doi.org/10.1016/s0960-9822(06)00055-8
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
9024623
Department(s)
Administration and Leadership
Document Type
Article