Abstract
HIV-1 infection results in a dementing illness affecting 20% of patients with AIDS. Several HIV-1 genes have been implicated in the pathogenesis of HIV-induced neurological disease. To search for distinct HIV-1 sequences associated with the development of dementia, brain-derived tat, env, and pol sequences were examined from AIDS patients defined pre-mortem as demented (HIV-D)[n=5] or non-demented (HIV-ND)[n=5]. Estimations of evolutionary distances and frequency of non-synonymous mutation rates revealed significant differences between brain-derived tat, env, and pol-encoded reverse transcriptase sequences. However, established zidovudine-associated resistance mutations in reverse transcriptase sequences were identified in only one HIV-D and one HIV-ND patient despite prolonged treatment of some patients. Non-synonymous/synonymous substitution rates among the fat sequences derived from patients with HIV-D were significantly higher compared to the HIV-ND group (P<0.001). The ratios of transversions to transitions were also significantly higher among the HIV-D tat sequences (P<0.01). Phylogenetic analyses showed clustering of sequences from each clinical group among the brain-derived tat and env sequences. These studies indicated that differing selective forces act on individual HIV-1 genes in the brain which may influence the development of dementia.
Original language | English (US) |
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Pages (from-to) | 387-393 |
Number of pages | 7 |
Journal | Journal of neurovirology |
Volume | 4 |
Issue number | 4 |
DOIs | |
State | Published - 1998 |
Keywords
- Dementia
- HIV-1
- Reverse transcriptase
- Tat
ASJC Scopus subject areas
- Neurology
- Clinical Neurology
- Cellular and Molecular Neuroscience
- Virology