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Brain-derived HIV-1 tat sequences from AIDS patients with dementia show increased molecular heterogeneity.

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 tat 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.

journal_name

J Neurovirol

journal_title

Journal of neurovirology

authors

Bratanich AC,Liu C,McArthur JC,Fudyk T,Glass JD,Mittoo S,Klassen GA,Power C

doi

10.3109/13550289809114537

subject

Has Abstract

pub_date

1998-08-01 00:00:00

pages

387-93

issue

4

eissn

1355-0284

issn

1538-2443

journal_volume

4

pub_type

杂志文章

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