Relationship between productive HIV-1 infection of macrophages and CCR5 utilization

HIV-1 isolates exhibit specificity for infection of immortalized T-cell lin es and macrophages. The distinct cellular tropisms have been attributed to expression of coreceptors CXCR4 or CCR5, respectively. However, it is uncle ar whether or not other tissue-specific determinants regulate entry. The cu rrent study uses a panel of viruses to analyze the relationship between CCR 5 utilization and macrophage infection. Only chimeric viruses with the enti re V3 loop from macrophage-tropic isolates, ADA or SF162, were able to infe ct macrophages. In contrast, chimeric viruses with smaller portions of the ADA V3 loop or the V3 loop of SF2, sufficient to allow CCR5 use, were insuf ficient for macrophage infection. PCR analysis showed that the defect in ma crophage infection of the latter viruses was due to a defect in entry. More over, strains capable of infecting macrophages showed relative resistance t o neutralization by anti-CCR5 antibody, 2D7, compared to strains which util ize CCR5 but are incapable of macrophage infection. (C) 1999 Academic Press .