Cd4-Independent Association Between Hiv-1 Gp120 and Cxcr4 - Functional Chemokine Receptors Are Expressed in Human Neurons

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 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. [References: 47]

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