Higher HIV-1 genetic diversity is associated with AIDS and neuropsychological impairment

George K. Hightower; Joseph K. Wong; Scott L. Letendre; Anya A. Umlauf; Ronald J. Ellis; Caroline C. Ignacio; Robert K. Heaton; Ann C. Collier; Christina M. Marra; David B. Clifford; Benjamin B. Gelman; Justin C. McArthur; Susan Morgello; David M. Simpson; J. A. McCutchan; Igor Grant; Susan J. Little; Douglas D. Richman; Sergei L. Kosakovsky Pond; Davey M. Smith

doi:10.1016/j.virol.2012.08.028

Higher HIV-1 genetic diversity is associated with AIDS and neuropsychological impairment

George K. Hightower, Joseph K. Wong, Scott L. Letendre, Anya A. Umlauf, Ronald J. Ellis, Caroline C. Ignacio, Robert K. Heaton, Ann C. Collier, Christina M. Marra, David B. Clifford, Benjamin B. Gelman, Justin C. McArthur, Susan Morgello, David M. Simpson, J. A. McCutchan, Igor Grant, Susan J. Little, Douglas D. Richman, Sergei L. Kosakovsky Pond, Davey M. Smith

Pathology

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

8 Scopus citations

Abstract

Standard methods used to estimate HIV-1 population diversity are often resource intensive (e.g., single genome amplification, clonal amplification and pyrosequencing) and not well suited for large study cohorts. Additional approaches are needed to address the relationships between intraindividual HIV-1 genetic diversity and 2 disease. With a small cohort of individuals, we validated three methods for measuring diversity: Shannon entropy and average pairwise distance (APD) using single genome sequences, and counts of mixed bases (i.e. ambiguous nucleotides) from population based sequences. In a large cohort, we then used the mixed base approach to determine associations between measure HIV-1 diversity and HIV associated disease. Normalized counts of mixed bases correlated with Shannon Entropy at both the nucleotide (rho=0.72, p=0.002) and amino acid level (rho=0.59, p=0.015), and APD (rho=0.75, p=0.001). Among participants who underwent neuropsychological and clinical assessments (n=187), increased HIV-1 population diversity was associated with both a diagnosis of AIDS and neuropsychological impairment.

Original language	English (US)
Pages (from-to)	498-505
Number of pages	8
Journal	Virology
Volume	433
Issue number	2
DOIs	https://doi.org/10.1016/j.virol.2012.08.028
State	Published - Nov 25 2012

Keywords

AIDS
Genetic diversity
HIV
Neuropsychological impairment
Viral population dynamics

ASJC Scopus subject areas

Virology

Access to Document

10.1016/j.virol.2012.08.028

Cite this

Hightower, G. K., Wong, J. K., Letendre, S. L., Umlauf, A. A., Ellis, R. J., Ignacio, C. C., Heaton, R. K., Collier, A. C., Marra, C. M., Clifford, D. B., Gelman, B. B., McArthur, J. C., Morgello, S., Simpson, D. M., McCutchan, J. A., Grant, I., Little, S. J., Richman, D. D., Kosakovsky Pond, S. L., & Smith, D. M. (2012). Higher HIV-1 genetic diversity is associated with AIDS and neuropsychological impairment. Virology, 433(2), 498-505. https://doi.org/10.1016/j.virol.2012.08.028

Hightower, GK, Wong, JK, Letendre, SL, Umlauf, AA, Ellis, RJ, Ignacio, CC, Heaton, RK, Collier, AC, Marra, CM, Clifford, DB, Gelman, BB, McArthur, JC, Morgello, S, Simpson, DM, McCutchan, JA, Grant, I, Little, SJ, Richman, DD, Kosakovsky Pond, SL & Smith, DM 2012, 'Higher HIV-1 genetic diversity is associated with AIDS and neuropsychological impairment', Virology, vol. 433, no. 2, pp. 498-505. https://doi.org/10.1016/j.virol.2012.08.028

@article{c11429f43ec84def9443fd3c6d3dcb9f,

title = "Higher HIV-1 genetic diversity is associated with AIDS and neuropsychological impairment",

abstract = "Standard methods used to estimate HIV-1 population diversity are often resource intensive (e.g., single genome amplification, clonal amplification and pyrosequencing) and not well suited for large study cohorts. Additional approaches are needed to address the relationships between intraindividual HIV-1 genetic diversity and 2 disease. With a small cohort of individuals, we validated three methods for measuring diversity: Shannon entropy and average pairwise distance (APD) using single genome sequences, and counts of mixed bases (i.e. ambiguous nucleotides) from population based sequences. In a large cohort, we then used the mixed base approach to determine associations between measure HIV-1 diversity and HIV associated disease. Normalized counts of mixed bases correlated with Shannon Entropy at both the nucleotide (rho=0.72, p=0.002) and amino acid level (rho=0.59, p=0.015), and APD (rho=0.75, p=0.001). Among participants who underwent neuropsychological and clinical assessments (n=187), increased HIV-1 population diversity was associated with both a diagnosis of AIDS and neuropsychological impairment.",

keywords = "AIDS, Genetic diversity, HIV, Neuropsychological impairment, Viral population dynamics",

author = "Hightower, {George K.} and Wong, {Joseph K.} and Letendre, {Scott L.} and Umlauf, {Anya A.} and Ellis, {Ronald J.} and Ignacio, {Caroline C.} and Heaton, {Robert K.} 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. A.} and Igor Grant and Little, {Susan J.} and Richman, {Douglas D.} and {Kosakovsky Pond}, {Sergei L.} and Smith, {Davey M.}",

note = "Funding Information: This work was supported by the Pendleton Foundation and National Institutes of Health Grants DA12065 , DA034978 , MH083552 , AI077304 , AI69432 , MH62512 , AI27670 , AI38858 , AI43638 , AI43752 , AI047745 , NS51132 , UCSD Centers for AIDS Research Translational Virology Core AI36214 , AI29164 , AI47745 , AI64086 , AI57167 and San Diego Veterans Affairs Healthcare System . ",

year = "2012",

month = nov,

day = "25",

doi = "10.1016/j.virol.2012.08.028",

language = "English (US)",

volume = "433",

pages = "498--505",

journal = "Virology",

issn = "0042-6822",

publisher = "Academic Press Inc.",

number = "2",

}

TY - JOUR

T1 - Higher HIV-1 genetic diversity is associated with AIDS and neuropsychological impairment

AU - Hightower, George K.

AU - Wong, Joseph K.

AU - Letendre, Scott L.

AU - Umlauf, Anya A.

AU - Ellis, Ronald J.

AU - Ignacio, Caroline C.

AU - Heaton, Robert K.

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. A.

AU - Grant, Igor

AU - Little, Susan J.

AU - Richman, Douglas D.

AU - Kosakovsky Pond, Sergei L.

AU - Smith, Davey M.

N1 - Funding Information: This work was supported by the Pendleton Foundation and National Institutes of Health Grants DA12065 , DA034978 , MH083552 , AI077304 , AI69432 , MH62512 , AI27670 , AI38858 , AI43638 , AI43752 , AI047745 , NS51132 , UCSD Centers for AIDS Research Translational Virology Core AI36214 , AI29164 , AI47745 , AI64086 , AI57167 and San Diego Veterans Affairs Healthcare System .

PY - 2012/11/25

Y1 - 2012/11/25

N2 - Standard methods used to estimate HIV-1 population diversity are often resource intensive (e.g., single genome amplification, clonal amplification and pyrosequencing) and not well suited for large study cohorts. Additional approaches are needed to address the relationships between intraindividual HIV-1 genetic diversity and 2 disease. With a small cohort of individuals, we validated three methods for measuring diversity: Shannon entropy and average pairwise distance (APD) using single genome sequences, and counts of mixed bases (i.e. ambiguous nucleotides) from population based sequences. In a large cohort, we then used the mixed base approach to determine associations between measure HIV-1 diversity and HIV associated disease. Normalized counts of mixed bases correlated with Shannon Entropy at both the nucleotide (rho=0.72, p=0.002) and amino acid level (rho=0.59, p=0.015), and APD (rho=0.75, p=0.001). Among participants who underwent neuropsychological and clinical assessments (n=187), increased HIV-1 population diversity was associated with both a diagnosis of AIDS and neuropsychological impairment.

AB - Standard methods used to estimate HIV-1 population diversity are often resource intensive (e.g., single genome amplification, clonal amplification and pyrosequencing) and not well suited for large study cohorts. Additional approaches are needed to address the relationships between intraindividual HIV-1 genetic diversity and 2 disease. With a small cohort of individuals, we validated three methods for measuring diversity: Shannon entropy and average pairwise distance (APD) using single genome sequences, and counts of mixed bases (i.e. ambiguous nucleotides) from population based sequences. In a large cohort, we then used the mixed base approach to determine associations between measure HIV-1 diversity and HIV associated disease. Normalized counts of mixed bases correlated with Shannon Entropy at both the nucleotide (rho=0.72, p=0.002) and amino acid level (rho=0.59, p=0.015), and APD (rho=0.75, p=0.001). Among participants who underwent neuropsychological and clinical assessments (n=187), increased HIV-1 population diversity was associated with both a diagnosis of AIDS and neuropsychological impairment.

KW - AIDS

KW - Genetic diversity

KW - HIV

KW - Neuropsychological impairment

KW - Viral population dynamics

UR - http://www.scopus.com/inward/record.url?scp=84867220683&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84867220683&partnerID=8YFLogxK

U2 - 10.1016/j.virol.2012.08.028

DO - 10.1016/j.virol.2012.08.028

M3 - Article

C2 - 22999095

AN - SCOPUS:84867220683

SN - 0042-6822

VL - 433

SP - 498

EP - 505

JO - Virology

JF - Virology

IS - 2

ER -

Higher HIV-1 genetic diversity is associated with AIDS and neuropsychological impairment

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this