Genetic features of cerebrospinal fluid-derived subtype B HIV-1 tat

Jun Yong Choi, George K. Hightower, Joseph K. Wong, Robert Heaton, Steven Woods, Igor Grant, Thomas D. Marcotte, Ronald J. Ellis, Scott L. Letendre, Ann C. Collier, Christina M. Marra, David B. Clifford, Benjamin B. Gelman, Justin C. McArthur, Susan Morgello, David M. Simpson, J. Allen McCutchan, Douglas D. Richman, Davey M. Smith

Research output: Contribution to journalArticle

9 Scopus citations

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 CSFderived 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.

Original languageEnglish (US)
Pages (from-to)81-90
Number of pages10
JournalJournal of neurovirology
Volume18
Issue number2
DOIs
StatePublished - Apr 1 2012

Keywords

  • Central nervous system
  • Compartmentalization
  • HIV
  • Tat

ASJC Scopus subject areas

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

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    Choi, J. Y., Hightower, G. K., Wong, J. K., Heaton, R., Woods, S., Grant, I., Marcotte, T. D., Ellis, R. J., Letendre, S. L., Collier, A. C., Marra, C. M., Clifford, D. B., Gelman, B. B., McArthur, J. C., Morgello, S., Simpson, D. M., McCutchan, J. A., Richman, D. D., & Smith, D. M. (2012). Genetic features of cerebrospinal fluid-derived subtype B HIV-1 tat. Journal of neurovirology, 18(2), 81-90. https://doi.org/10.1007/s13365-011-0059-9