Enhancement of human immunodeficiency virus type 1 infection by the CC-chemokine RANTES is independent of the mechanism of virus-cell fusion

We have studied the effects of CC-chemokines on human immunodeficiency viru s type 1 (HIV-1) infection, focusing on the infectivity enhancement caused by RANTES. High RANTES concentrations increase the infectivity of HIV-1 iso lates that use CXC-chemokine receptor 3 for entry. However, RANTES can have a similar enhancing effect on macrophagetropic viruses that enter via CC-c hemokine receptor 5 (CCRS), despite binding to the same receptor as the vir us. Furthermore, RANTES enhances the infectivity of HIV-1 pseudotyped with the envelope glycoprotein of murine leukemia virus or vesicular stomatitis virus, showing that the mechanism of enhancement is independent of the rout e of virus-cell fusion. The enhancing effects of RANTES are not mediated vi a CCR5 or other known chemokine receptors and are not mimicked by MIP-1 alp ha or MIP-1 beta. The N-terminally modified derivative aminooxypentane RANT ES (AOP-RANTES) efficiently inhibits HIV-1 infection via CCRS but otherwise mimics RANTES by enhancing viral infectivity. There are two mechanisms of enhancement: one apparent when target cells are pretreated with RANTES (or AOP-RANTES) for several hours, and the other apparent when RANTES (or AOP-R ANTES) is added during virus-cell absorption. We believe that the first mec hanism is related to cellular activation by RANTES, whereas the second is a n increase in virion attachment to target cells.