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

A. C. Bratanich, C. Liu, J. C. McArthur, T. Fudyk, J. D. Glass, S. Mittoo, G. A. Klassen, C. Power

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)387-393
Number of pages7
JournalJournal of neurovirology
Volume4
Issue number4
DOIs
StatePublished - Jan 1 1998

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Keywords

  • Dementia
  • HIV-1
  • Reverse transcriptase
  • Tat

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Virology

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