T cell-tropic HIV gp120 mediates CD4 and CD8 cell chemotaxis through CXCR4 independent of CD4: implications for HIV pathogenesis.
HIV entry is determined by one or more chemokine receptors. T cell-tropic viruses bind CXCR4, whereas macrophage-tropic viruses use CCR5 and other CCRs. Infection with CXCR4 and CCR5-tropic HIV requires initial binding to CD4, and chemotaxis induced by the CCR5-tropic envelope has been reported to be strictly dependent on CD4 binding. We demonstrate that, in contrast to CD4-dependent gp120 signaling via CCR5, envelope signaling through CXCR4 is CD4 independent, inducing chemotaxis of both CD4 and CD8 T cells. Signaling by virus or soluble envelope through CXCR4 may affect pathogenesis by attracting and activating target and effector cells.
Iyengar
S
S
Department of Molecular Microbiology and Immunology, School of Hygiene Johns Hopkins University, Baltimore, MD 21205, USA.
Schwartz
D H
DH
Hildreth
J E
JE
D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000821:virology; D002634:Chemotaxis, Leukocyte; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000209:etiology*; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D008264:Macrophages / Q000821:virology; D011485:Protein Binding; D019718:Receptors, CXCR4 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000821:virology; D013601:T-Lymphocytes / Q000821:virology*
D015699:HIV Envelope Protein gp120; D019718:Receptors, CXCR4; D011994:Recombinant Proteins