Pathogenesis And Immunology Of Animal And Human Retroviruses

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Human immunodeficiency viruses of various subtypes appear to have different patterns of spread in tissues of infected patients. In a patient with a dual HIV infection involving both subtype- A and C virus strains, it was previously noted that the subtype-C virus was in both the cervix and the blood, whereas subtype-A virus was only in blood. We hypothesized that envelope sequence differences between these viruses might explain this different organ tropism. Therefore, the envelope sequences form V1 through V3 regions were amplified and cloned into infectious molecular clones. Laboratory studies showed that the sequences from subtype-C facilitated faster replication in PBMC cultures as well as more extensive fusion of HeLa CD4 CCR5 cells compared to subtype-A clones. Two amino acid sequence differences between A and C clones in the V1 and V3 regions appeared to account for these differences. Although subtype-A clones initially grew slowly in PBMC, after 4-6 days these viruses grew faster, and it was found that the viruses had acquired mutations mimicking those found in the subtype-C clones. The envelope residues at these same sites were noted to be prevalent in the sequences of most subtype-A or subtype-C viruses from patients in all parts of the world. Therefore, these data suggest a possible role for these sequences in influencing infection efficiency and organ tropism in vivo.