CD4-independent association between HIV-1 gp120 and CXCR4: functional chemokine receptors are expressed in human neurons

Curr Biol. 1997 Feb 1;7(2):112-21. doi: 10.1016/s0960-9822(06)00055-8.


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.

MeSH terms

  • Adult
  • Animals
  • Binding, Competitive
  • Brain / physiology*
  • CD4 Antigens / physiology
  • CHO Cells
  • Cell Line
  • Cells, Cultured
  • Chemokine CXCL12
  • Chemokines / metabolism
  • Chemokines / pharmacology*
  • Chemokines, CXC*
  • Chemotaxis
  • Cricetinae
  • Fetus
  • GTP-Binding Proteins / physiology
  • HIV Envelope Protein gp120 / metabolism*
  • HIV-1 / physiology*
  • Humans
  • Kidney
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / physiology*
  • Neurons / immunology
  • Neurons / physiology*
  • Receptors, CXCR4
  • Receptors, HIV / biosynthesis
  • Receptors, HIV / physiology*


  • CD4 Antigens
  • CXCL12 protein, human
  • Chemokine CXCL12
  • Chemokines
  • Chemokines, CXC
  • HIV Envelope Protein gp120
  • Membrane Proteins
  • Receptors, CXCR4
  • Receptors, HIV
  • GTP-Binding Proteins