Coreceptor ligand inhibition of fetal brain cell infection by HIV type 1

The capacity of a panel of HIV-1 isolates to infect primary mixed fetal bra in cell cultures was estimated and their sensitivity to inhibition by a ran ge of coreceptor ligands assessed. Our results show that (1) HIV-1 strains that predominantly use CCR5 or only CXCR4 are able to infect microglia in p rimary brain cell cultures, and (2) ligands to these two coreceptors can in hibit brain cell infection. CCR5 ligands (including AOP-RANTES, a potent in hibitor of CCR5-dependent infection), however, blocked infection only weakl y, raising the possibility that alternative unidentified coreceptors are al so used. Interestingly, vMIP-II, a chemokine encoded by the Kaposi sarcoma-associate d herpes virus (KSHV), reduced brain cell infection by all HIV-1. strains t ested, including both R5 and X4 viruses. Our results therefore indicate tha t novel drugs targeted to the major HIV-1 coreceptors will influence HIV re plication in the brain, if they cross the blood-brain barrier.