Genetic features of cerebrospinal fluid-derived subtype B HIV-1 tat.
Title | Genetic features of cerebrospinal fluid-derived subtype B HIV-1 tat. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Choi, 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 Authors | CHARTER Group |
Journal | J Neurovirol |
Volume | 18 |
Issue | 2 |
Pagination | 81-90 |
Date Published | 2012 Apr |
ISSN | 1538-2443 |
Keywords | Adult, 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. |
DOI | 10.1007/s13365-011-0059-9 |
Alternate Journal | J. Neurovirol. |
PubMed ID | 22528397 |
PubMed Central ID | PMC3572198 |
Grant List | U19AI090970 / 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 |