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

doi:10.1007/s13365-011-0059-9

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

Pathology

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

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 language	English (US)
Pages (from-to)	81-90
Number of pages	10
Journal	Journal of neurovirology
Volume	18
Issue number	2
DOIs	https://doi.org/10.1007/s13365-011-0059-9
State	Published - Apr 2012

Keywords

Central nervous system
Compartmentalization
HIV
Tat

ASJC Scopus subject areas

Neurology
Clinical Neurology
Cellular and Molecular Neuroscience
Virology

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10.1007/s13365-011-0059-9

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Choi, J. Y., Hightower, G. K., Wong, J. K., Heaton, R., Woods, S., Grant, I., Marcotte, T. D., Ellis, R. J., Letendre, S. L., Collier, A. C., Marra, C. M., Clifford, D. B., Gelman, B. B., McArthur, J. C., Morgello, S., Simpson, D. M., McCutchan, J. A., Richman, D. D., & Smith, D. M. (2012). Genetic features of cerebrospinal fluid-derived subtype B HIV-1 tat. Journal of neurovirology, 18(2), 81-90. https://doi.org/10.1007/s13365-011-0059-9

Choi, JY, 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, McCutchan, JA, Richman, DD & Smith, DM 2012, 'Genetic features of cerebrospinal fluid-derived subtype B HIV-1 tat', Journal of neurovirology, vol. 18, no. 2, pp. 81-90. https://doi.org/10.1007/s13365-011-0059-9

@article{11f80d3ac3e54e978fb8823279c3612f,

title = "Genetic features of cerebrospinal fluid-derived subtype B HIV-1 tat",

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.",

keywords = "Central nervous system, Compartmentalization, HIV, Tat",

author = "Choi, {Jun Yong} and Hightower, {George K.} and Wong, {Joseph K.} and Robert Heaton and Steven Woods and Igor Grant and Marcotte, {Thomas D.} and Ellis, {Ronald J.} and Letendre, {Scott L.} and Collier, {Ann C.} and Marra, {Christina M.} and Clifford, {David B.} and Gelman, {Benjamin B.} and McArthur, {Justin C.} and Susan Morgello and Simpson, {David M.} and McCutchan, {J. Allen} and Richman, {Douglas D.} and Smith, {Davey M.}",

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). ",

year = "2012",

month = apr,

doi = "10.1007/s13365-011-0059-9",

language = "English (US)",

volume = "18",

pages = "81--90",

journal = "Journal of neurovirology",

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T1 - Genetic features of cerebrospinal fluid-derived subtype B HIV-1 tat

AU - Choi, Jun Yong

AU - Hightower, George K.

AU - Wong, Joseph K.

AU - Heaton, Robert

AU - Woods, Steven

AU - Grant, Igor

AU - Marcotte, Thomas D.

AU - Ellis, Ronald J.

AU - Letendre, Scott L.

AU - Collier, Ann C.

AU - Marra, Christina M.

AU - Clifford, David B.

AU - Gelman, Benjamin B.

AU - McArthur, Justin C.

AU - Morgello, Susan

AU - Simpson, David M.

AU - McCutchan, J. Allen

AU - Richman, Douglas D.

AU - Smith, Davey M.

N1 - 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).

PY - 2012/4

Y1 - 2012/4

N2 - 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.

AB - 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.

KW - Central nervous system

KW - Compartmentalization

KW - HIV

KW - Tat

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U2 - 10.1007/s13365-011-0059-9

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SP - 81

EP - 90

JO - Journal of neurovirology

JF - Journal of neurovirology

IS - 2

ER -

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

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Keywords

ASJC Scopus subject areas

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