DEMENTED AND NONDEMENTED PATIENTS WITH AIDS DIFFER IN BRAIN-DERIVED HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE SEQUENCES

Human immunodeficiency virus (HIV) dementia is a common clinical syndr ome of uncertain pathogenesis in patients with AIDS. In several animal models of retrovirus-induced brain disease, specific viral envelope s equences have been found to influence the occurrence of central nervou s system disease. Therefore, to search for unique envelope sequences c orrelated with HIV dementia, we studied 22 HIV-infected patients who w ere neurologically assessed premortem and classified into demented (HI VD) (n = 14) and nondemented (ND) (n = 8) groups. Using DNA from autop sied brain and spleen, we amplified, cloned, and sequenced a 430-nucle otide region including the V3 loop and flanking regions. All brain-der ived clones in both clinical groups showed marked homology to the macr ophage-tropic consensus sequence within the V3 loop. Two amino acid po sitions within (position 305) and outside (position 329) the V3 region showed significant divergence between the two clinical groups. At pos ition 305, a histidine was predominant in the HIVD group and was not o bserved in the ND group, but a proline was predominant in the ND group and was not observed in the HIVD group. Similarly, at position 329, a leucine was predominant in the HIVD group but rarely observed in the ND group,whereas an isoleucine,vas predominant in the ND group at this position. In addition, the HIVD group had 21 amino acid residues at s pecific positions that were unique relative to the ND group, whereas o nly 2 residues at specific positions were unique to the ND group. Thes e data suggest that distinct HIV envelope sequences are associated wit h the clinical expression of HIV dementia.