Résumé
Chemokines and chemokine receptors play important roles in HIV-1
infection and tropism. CCR5 is the major macrophage-tropic coreceptor
for HIV-1 whereas CXC chemokine receptor 4 (CXCR4) serves the
counterpart function for T cell-tropic viruses. An outstanding
biological mystery is why only R5-HIV-1 is initially detected in new
seroconvertors who are exposed to R5 and X4 viruses. Indeed, X4 virus
emerges in a minority of patients and only in the late stage of
disease, suggesting that early negative selection against HIV-1–CXCR4
interaction may exist. Here, we report that the HIV-1 Tat protein,
which is secreted from virus-infected cells, is a CXCR4-specific
antagonist. Soluble Tat selectively inhibited the entry and replication
of X4, but not R5, virus in peripheral blood mononuclear cells (PBMCs).
We propose that one functional consequence of secreted Tat is to select
against X4 viruses, thereby influencing the early in
vivo course of HIV-1 disease.