Date Published:
2012 Apr

Publication Type:
Journal Article

Authors:

J.Yong Choi
G.K. Hightower
J.K. Wong
R. Heaton
S. Woods
I. Grant
T.D. Marcotte
R.J. Ellis
S.L. Letendre
A.C. Collier
C.M. Marra
D.B. Clifford
B.B. Gelman
J.C. McArthur
S. Morgello
D.M. Simpson
A. McCutchan
D.D. Richman
D.M. Smith

Secondary:
J Neurovirol

Volume:
18

Pagination:
81-90

Issue:
2

PMID:
22528397

URL:
https://pubmed.ncbi.nlm.nih.gov/22528397

DOI:
10.1007/s13365-011-0059-9

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:
<p>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.</p>