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 journalArticlepeer-review

11 Citations (Scopus)

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
Pages (from-to)81-90
Number of pages10
JournalJournal of NeuroVirology
Volume18
Issue number2
DOIs
Publication statusPublished - 2012 Apr

Bibliographical note

Funding Information:
This work was supported by grants from the National Institutes of Health: MH22005, AI69432, AI043638, MH62512, MH083552, AI077304, AI36214, AI047745, AI74621, AI080353, U19AI090970 and the James B. Pendleton Charitable Trust. This work was supported by the National Research Foundation of Korea Grant funded by the Korean Government (NRF-2011-220-E00015) and a faculty research grant of Yonsei University College of Medicine for 2011 (6-2011-0115).

All Science Journal Classification (ASJC) codes

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

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