C. Power et al., DEMENTED AND NONDEMENTED PATIENTS WITH AIDS DIFFER IN BRAIN-DERIVED HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE SEQUENCES, Journal of virology, 68(7), 1994, pp. 4643-4649
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.