CHEMOKINE RECEPTOR UTILIZATION BY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1ISOLATES THAT REPLICATE IN MICROGLIA

The role of human immunodeficiency virus (HIV) strain variability rema ins a key unanswered question in HIV dementia, a condition affecting a round 20% of infected individuals. Several groups have shown that viru ses within the central nervous system (CNS) of infected patients const itute an independently evolving subset of HIV strains. A potential exp lanation for the replication and sequestration of viruses within the C NS is the preferential use of certain chemokine receptors present in m icroglia. To determine the role of specific chemokine coreceptors in i nfection of adult microglial cells, we obtained a small panel of HIV t ype 1 brain isolates, as well as other HIV strains that replicate well in cultured microglial cells. These viruses and molecular clones of t heir envelopes were used in infections, in cell-to-cell fusion assays, and in the construction of pseudotypes. The results demonstrate the p redominant use of CCR5, at least among the major coreceptors, with min or use of CCR3 and CXCR4 by some of the isolates or their envelope clo nes.