Relationship between productive HIV-1 infection of macrophages and CCR5 utilization.
HIV-1 isolates exhibit specificity for infection of immortalized T-cell lines and macrophages. The distinct cellular tropisms have been attributed to expression of coreceptors CXCR4 or CCR5, respectively. However, it is unclear whether or not other tissue-specific determinants regulate entry. The current study uses a panel of viruses to analyze the relationship between CCR5 utilization and macrophage infection. Only chimeric viruses with the entire V3 loop from macrophage-tropic isolates, ADA or SF162, were able to infect 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 insufficient for macrophage infection. PCR analysis showed that the defect in macrophage infection of the latter viruses was due to a defect in entry. Moreover, strains capable of infecting macrophages showed relative resistance to neutralization by anti-CCR5 antibody, 2D7, compared to strains which utilize CCR5 but are incapable of macrophage infection.
Hung
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CS
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, 63110, USA.
Pontow
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Ratner
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D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D004279:DNA, Viral / Q000032:analysis; D005434:Flow Cytometry; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000821:virology; D008264:Macrophages / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D019713:Receptors, CCR5 / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism; D011995:Recombination, Genetic
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D004279:DNA, Viral; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D019713:Receptors, CCR5; D019718:Receptors, CXCR4