RANTES stimulates cell-mediated transmission of HIV-1 infection

We wished to determine the effects of the beta-chemokine RANTES in an estab lished system of cell-mediated transmission of HIV-1, that is, normal human umbilical vein endothelial cells (HUVEC) nonproductively infected with HIV -1, cocultivated with CD4(+) T cells to rescue productive infection. The re sults indicate that the addition of RANTES to HUVEC, either before or after HIV-1 infection, stimulates HIV-1 rescue by CD4(+) T cells. However, viral DNA is not increased in HUVEC, suggesting that the stinnulation exerted by RANTES could be mediated by events following HUVEC infection. The mechanis ms of increase seem to be related to the rescue phase, involving membrane i nteraction of abortively infected HUVEC with permissive T cells. In fact, a strong upregulation and polarization of intercellular adhesion molecule-1 (ICAM-1) is induced in HUVEC by RANTES, and antibodies against BCAM-1 inhib it HIV-1 rescue by T cells. These results indicate that RANTES, similarly t o other inflammatory cytokines, may favor HIV-1 spreading and crossing of b lood-tissue barriers by indirect mechanisms involving membrane interactions between nonproductively infected and permissive cells.