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

TitleGenetic features of cerebrospinal fluid-derived subtype B HIV-1 tat.
Publication TypeJournal Article
Year of Publication2012
AuthorsChoi, JYong, Hightower, GK, Wong, JK, Heaton, R, Woods, S, Grant, I, Marcotte, TD, Ellis, RJ, Letendre, SL, Collier, AC, Marra, CM, Clifford, DB, Gelman, BB, McArthur, JC, Morgello, S, Simpson, DM, J McCutchan, A, Richman, DD, Smith, DM
Corporate AuthorsCHARTER Group
JournalJ Neurovirol
Volume18
Issue2
Pagination81-90
Date Published2012 Apr
ISSN1538-2443
KeywordsAdult, AIDS Dementia Complex, Artificial Intelligence, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, CHARTER, Female, Genetic Heterogeneity, HIV-1, Humans, Internal, Male, Middle Aged, Mutation, Nucleic Acid Conformation, Protein Structure, Tertiary, RNA, Viral, Sequence Analysis, DNA, tat Gene Products, Human Immunodeficiency Virus, Viral Tropism
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.

DOI10.1007/s13365-011-0059-9
Alternate JournalJ. Neurovirol.
PubMed ID22528397
PubMed Central IDPMC3572198
Grant ListU19AI090970 / AI / NIAID NIH HHS / United States
R21 AI077304 / AI / NIAID NIH HHS / United States
AI043638 / AI / NIAID NIH HHS / United States
R01 AI047745 / AI / NIAID NIH HHS / United States
UM1 AI069432 / AI / NIAID NIH HHS / United States
AI080353 / AI / NIAID NIH HHS / United States
AI047745 / AI / NIAID NIH HHS / United States
AI36214 / AI / NIAID NIH HHS / United States
MH083552 / MH / NIMH NIH HHS / United States
R21 AI047745 / AI / NIAID NIH HHS / United States
U01 AI069432 / AI / NIAID NIH HHS / United States
AI74621 / AI / NIAID NIH HHS / United States
U01 AI043638 / AI / NIAID NIH HHS / United States
N01MH22005 / MH / NIMH NIH HHS / United States
R56 AI047745 / AI / NIAID NIH HHS / United States
P30 AI027763 / AI / NIAID NIH HHS / United States
P30 MH062512 / MH / NIMH NIH HHS / United States
R21 AI080353 / AI / NIAID NIH HHS / United States
MH62512 / MH / NIMH NIH HHS / United States
P30 AI036214 / AI / NIAID NIH HHS / United States
N01 MH022005 / MH / NIMH NIH HHS / United States
R01 MH083552 / MH / NIMH NIH HHS / United States
AI077304 / AI / NIAID NIH HHS / United States
U19 AI090970 / AI / NIAID NIH HHS / United States
AI69432 / AI / NIAID NIH HHS / United States
P01 AI074621 / AI / NIAID NIH HHS / United States
R24 AI106039 / AI / NIAID NIH HHS / United States