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- Title
Genetic features of cerebrospinal fluid-derived subtype B HIV-1 tat.
- Authors
Choi, Jun Yong; Hightower, George K; Wong, Joseph K; Heaton, Robert; Woods, Steven; Grant, Igor; Marcotte, Thomas D; Ellis, Ronald J; Letendre, Scott L; Collier, Ann C; Marra, Christina M; Clifford, David B; Gelman, Benjamin B; McArthur, Justin C; Morgello, Susan; Simpson, David M; McCutchan, J Allen; Richman, Douglas D; Smith, Davey M; Charter Group
- Abstract
Since HIV-1 Tat has been associated with neurocognitive dysfunction, we investigated 60 HIV-1 subtype B-infected individuals who were characterized for neurocognitive functioning and had paired CSF and blood plasma samples available. To avoid issues with repeated sampling, we generated population-based HIV-1 tat sequences from each compartment and evaluated these data using a battery of phylogenetic, statistical, and machine learning tools. These analyses identified position HXB2 5905 within the cysteine-rich domain of tat as a signature of CSF-derived HIV-1, and a higher number of mixed bases in CSF, as measure of diversity, was associated with HIV-associated neurocognitive disorder. Since identified mutations were synonymous, we evaluated the predicted secondary RNA structures, which showed that this mutation altered secondary structure. As a measure of divergence, the genetic distance between the blood and CSF-derived tat was inversely correlated with current and nadir CD4+ T cell counts. These data suggest that specific HIV-1 features of tat influence neurotropism and neurocognitive impairment.
- Publication
Journal of neurovirology, 2012, Vol 18, Issue 2, p81
- ISSN
1538-2443
- Publication type
Journal Article
- DOI
10.1007/s13365-011-0059-9