MACROPHAGE-TROPIC VARIANTS INITIATE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION AFTER SEXUAL, PARENTERAL, AND VERTICAL TRANSMISSION

Macrophage-tropic, non-syncytium-inducing, HIV-1 variants predominate in the asymptomatic phase of infection and may be responsible for esta blishing infection in an individual exposed to the mixture of HIV-1 va riants. Here, genotypical and phenotypical characteristics of virus po pulations, present in sexual, parenteral, or vertical donor-recipient pairs, were studied. Sequence analysis of the V3 domain confirmed the presence of a homogeneous virus population in recently infected indivi duals. Biological HIV-1 clones were further characterized for syncytiu m inducing capacity on the MT2 cell line and for macrophage tropism as defined by the appearance of proviral DNA upon inoculation of monocyt e-derived macrophages. Both sexual and parenteral transmission cases r evealed a selective outgrowth in the recipient of the most macrophage- tropic variant(s) present in the donor. In three out of five vertical transmission cases, more than one highly macrophage-tropic virus varia nt was present in the child shortly after birth, suggestive of transmi ssion of multiple variants. In three primary infection cases, homogene ous virus populations of macrophage-tropic, non-syncytium-inducing var iants were present prior to seroconversion, thus excluding humoral imm unity as the selective pressure in favour of macrophage-tropic variant s. These observations may have important implications for vaccine deve lopment.