Demented and nondemented patients with AIDS differ in brain-derived human immunodeficiency virus type 1 envelope sequences

Abstract

Human immunodeficiency virus (HIV) dementia is a common clinical syndrome of uncertain pathogenesis in patients with AIDS. In several animal models of retrovirus-induced brain disease, specific viral envelope sequences have been found to influence the occurrence of central nervous system disease. Therefore, to search for unique envelope sequences correlated with HIV dementia, we studied 22 HIV-infected patients who were neurologically assessed premortem and classified into demented (HIVD) (n = 14) and nondemented (ND) (n = 8) groups. Using DNA from autopsied brain and spleen, we amplified, cloned, and sequenced a 430-nucleotide region including the V3 loop and flanking regions. All brain-derived clones in both clinical groups showed marked homology to the macrophage-tropic consensus sequence within the V3 loop. Two amino acid positions within (position 305) and outside (position 329) the V3 region showed significant divergence between the two clinical groups. At position 305, a histidine was predominant in the HIVD group and was not observed 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 was predominant in the ND group at this position. In addition, the HIVD group had 21 amino acid residues at specific positions that were unique relative to the ND group, whereas only 2 residues at specific positions were unique to the ND group. These data suggest that distinct HIV envelope sequences are associated with the clinical expression of HIV dementia.