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J Neurovirol. 2012 Apr;18(2):81-90. doi: 10.1007/s13365-011-0059-9. Epub 2012 Apr 13.

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

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1
Department of Internal Medicine and AIDS Research Institute, Yonsei University College of Medicine, 250 Seongsanno, Seodaemun-gu, Seoul 120-752, South Korea. seran@yuhs.ac

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.

PMID:
22528397
PMCID:
PMC3572198
DOI:
10.1007/s13365-011-0059-9
[Indexed for MEDLINE]
Free PMC Article

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