Consistent and significant inhibition of human immunodeficiency virus type1 envelope-mediated membrane fusion by beta-chemokines (RANTES) in primaryhuman macrophages

Citation
Ts. Stantchev et Cc. Broder, Consistent and significant inhibition of human immunodeficiency virus type1 envelope-mediated membrane fusion by beta-chemokines (RANTES) in primaryhuman macrophages, J INFEC DIS, 182(1), 2000, pp. 68-78
Citations number
100
Categorie Soggetti
Clinical Immunolgy & Infectious Disease",Immunology
Journal title
JOURNAL OF INFECTIOUS DISEASES
ISSN journal
00221899 → ACNP
Volume
182
Issue
1
Year of publication
2000
Pages
68 - 78
Database
ISI
SICI code
0022-1899(200007)182:1<68:CASIOH>2.0.ZU;2-Y
Abstract
Infection and entry of CD4(+) cells by human immunodeficiency virus type 1 (HIV-1) requires a coreceptor molecule, which, in concert with CD4, interac ts with the viral envelope glycoprotein (Env), leading to membrane fusion, The principal coreceptors are the CCR5 and CXCR4 chemokine receptors. The s uppressive effect of beta-chemokines, principally RANTES, on certain HIV-1 isolates was established before the discovery of the CCR5 receptor, and the re have since been multiple reports confirming this initial observation. Ho wever, the inhibitory effect of beta-chemokines on HIV-1 infection of macro phages has been controversial. The current study focused on this issue in d etail, with a reductionist approach, using assays that measure the effect o f beta-chemokines solely on Env-mediated fusion. It is shown that under a v ariety of culture and differentiation conditions, RANTES maintains a signif icant and consistent inhibitory effect on CCR5-dependent Env-mediated fusio n, and the role of these findings is discussed in relation to the role of b eta-chemokines in HIV pathogenesis.