Consistent and significant inhibition of human immunodeficiency virus type 1 envelope-mediated membrane fusion by beta-chemokines (RANTES) in primary human macrophages.
Infection and entry of CD4(+) cells by human immunodeficiency virus type 1 (HIV-1) requires a coreceptor molecule, which, in concert with CD4, interacts with the viral envelope glycoprotein (Env), leading to membrane fusion. The principal coreceptors are the CCR5 and CXCR4 chemokine receptors. The suppressive effect of beta-chemokines, principally RANTES, on certain HIV-1 isolates was established before the discovery of the CCR5 receptor, and there have since been multiple reports confirming this initial observation. However, the inhibitory effect of beta-chemokines on HIV-1 infection of macrophages has been controversial. The current study focused on this issue in detail, with a reductionist approach, using assays that measure the effect of beta-chemokines solely on Env-mediated fusion. It is shown that under a variety of culture and differentiation conditions, RANTES maintains a significant and consistent inhibitory effect on CCR5-dependent Env-mediated fusion, and the role of these findings is discussed in relation to the role of beta-chemokines in HIV pathogenesis.
Stantchev
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Department of Microbiology and Immunology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799, USA. tstanchev@mxb.usuhs.mil
Broder
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D018946:Chemokine CCL5 / Q000494:pharmacology*; D019742:Chemokines, CC / Q000494:pharmacology; D019743:Chemokines, CXC / Q000494:pharmacology; D004347:Drug Interactions; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D015699:HIV Envelope Protein gp120 / Q000187:drug effects / Q000502:physiology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology / Q000821:virology; D008561:Membrane Fusion / Q000187:drug effects*
D018946:Chemokine CCL5; D019742:Chemokines, CC; D019743:Chemokines, CXC; D015699:HIV Envelope Protein gp120; D016178:Granulocyte-Macrophage Colony-Stimulating Factor