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