Evolution of human immunodeficiency virus type 1 in relation to disease progression in children

Nataly Strunnikova, Stuart C. Ray, Christina Lancioni, Man Nguyen, Raphael P. Viscidi

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Objective: To compare patterns of nonsynonymous and synonymous substitutions over time in the V1V2 and C2V3 regions of human immunodeficiency virus type 1 (HIV-1) env and in a conserved segment of pol in HIV-1-infected children with varying rates of CD4+ T-cell decline. Study Design/Methods: Longitudinal study of HIV-1 genetic variants sampled from peripheral blood of 3 children affected with acquired immunodeficiency syndrome (AIDS) and 4 children with slow disease progression. Nested polymerase chain reaction (PCR) was used to detect HIV-1 genetic material in plasma-derived virions and cellular DNA. Sequence variants were enumerated by screening cloned PCR products using heteroduplex mobility assay (HMA) or single-strand conformation polymorphism analysis (SSCP) and nucleotide sequencing. Frequencies of nonsynonymous and synonymous substitutions within sampling points and the accumulation rate of nucleotide substitutions over the period of observation were calculated. Results: In the C2V3 region, higher rates of accumulation of nonsynonymous substitutions were associated with more precipitous declines in CD4+ cell numbers. In the V1V2 region, rates of accumulation of nonsynonymous substitutions were comparable with those in the C2V3 region, but similar rates were observed in AIDS-affected children and children with slow disease progression. The rate of accumulation of nonsynonymous substitutions in the pol region was lower than that in the C2V3 and V1V2 regions. Conclusions: Rates of accumulation of nucleotide substitutions vary across the HIV-1 genome and differ in relation to disease progression in children. The finding of greater rates of non-synonymous substitution in the immunodominant C2V3 region in children whose disease progressed rapidly is consistent with a vigorous but inadequate immune response in children who are unable to control HIV-1 infection.

Original languageEnglish (US)
Pages (from-to)224-239
Number of pages16
JournalJournal of Human Virology
Volume1
Issue number3
StatePublished - Mar 1998
Externally publishedYes

Fingerprint

Disease Progression
HIV-1
Nucleotides
Acquired Immunodeficiency Syndrome
X-Linked Combined Immunodeficiency Diseases
Immunodominant Epitopes
Polymerase Chain Reaction
Virus Diseases
Virion
Longitudinal Studies
Cell Count
Observation
Genome
T-Lymphocytes
DNA
Genes

Keywords

  • Disease progression
  • HIV-1
  • Molecular evolution
  • Pediatric HIV infection

ASJC Scopus subject areas

  • Virology

Cite this

Evolution of human immunodeficiency virus type 1 in relation to disease progression in children. / Strunnikova, Nataly; Ray, Stuart C.; Lancioni, Christina; Nguyen, Man; Viscidi, Raphael P.

In: Journal of Human Virology, Vol. 1, No. 3, 03.1998, p. 224-239.

Research output: Contribution to journalArticle

Strunnikova, Nataly ; Ray, Stuart C. ; Lancioni, Christina ; Nguyen, Man ; Viscidi, Raphael P. / Evolution of human immunodeficiency virus type 1 in relation to disease progression in children. In: Journal of Human Virology. 1998 ; Vol. 1, No. 3. pp. 224-239.
@article{7aa100b3f0014de8a32ff356e5baa05e,
title = "Evolution of human immunodeficiency virus type 1 in relation to disease progression in children",
abstract = "Objective: To compare patterns of nonsynonymous and synonymous substitutions over time in the V1V2 and C2V3 regions of human immunodeficiency virus type 1 (HIV-1) env and in a conserved segment of pol in HIV-1-infected children with varying rates of CD4+ T-cell decline. Study Design/Methods: Longitudinal study of HIV-1 genetic variants sampled from peripheral blood of 3 children affected with acquired immunodeficiency syndrome (AIDS) and 4 children with slow disease progression. Nested polymerase chain reaction (PCR) was used to detect HIV-1 genetic material in plasma-derived virions and cellular DNA. Sequence variants were enumerated by screening cloned PCR products using heteroduplex mobility assay (HMA) or single-strand conformation polymorphism analysis (SSCP) and nucleotide sequencing. Frequencies of nonsynonymous and synonymous substitutions within sampling points and the accumulation rate of nucleotide substitutions over the period of observation were calculated. Results: In the C2V3 region, higher rates of accumulation of nonsynonymous substitutions were associated with more precipitous declines in CD4+ cell numbers. In the V1V2 region, rates of accumulation of nonsynonymous substitutions were comparable with those in the C2V3 region, but similar rates were observed in AIDS-affected children and children with slow disease progression. The rate of accumulation of nonsynonymous substitutions in the pol region was lower than that in the C2V3 and V1V2 regions. Conclusions: Rates of accumulation of nucleotide substitutions vary across the HIV-1 genome and differ in relation to disease progression in children. The finding of greater rates of non-synonymous substitution in the immunodominant C2V3 region in children whose disease progressed rapidly is consistent with a vigorous but inadequate immune response in children who are unable to control HIV-1 infection.",
keywords = "Disease progression, HIV-1, Molecular evolution, Pediatric HIV infection",
author = "Nataly Strunnikova and Ray, {Stuart C.} and Christina Lancioni and Man Nguyen and Viscidi, {Raphael P.}",
year = "1998",
month = "3",
language = "English (US)",
volume = "1",
pages = "224--239",
journal = "Journal of Human Virology",
issn = "1090-9508",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - Evolution of human immunodeficiency virus type 1 in relation to disease progression in children

AU - Strunnikova, Nataly

AU - Ray, Stuart C.

AU - Lancioni, Christina

AU - Nguyen, Man

AU - Viscidi, Raphael P.

PY - 1998/3

Y1 - 1998/3

N2 - Objective: To compare patterns of nonsynonymous and synonymous substitutions over time in the V1V2 and C2V3 regions of human immunodeficiency virus type 1 (HIV-1) env and in a conserved segment of pol in HIV-1-infected children with varying rates of CD4+ T-cell decline. Study Design/Methods: Longitudinal study of HIV-1 genetic variants sampled from peripheral blood of 3 children affected with acquired immunodeficiency syndrome (AIDS) and 4 children with slow disease progression. Nested polymerase chain reaction (PCR) was used to detect HIV-1 genetic material in plasma-derived virions and cellular DNA. Sequence variants were enumerated by screening cloned PCR products using heteroduplex mobility assay (HMA) or single-strand conformation polymorphism analysis (SSCP) and nucleotide sequencing. Frequencies of nonsynonymous and synonymous substitutions within sampling points and the accumulation rate of nucleotide substitutions over the period of observation were calculated. Results: In the C2V3 region, higher rates of accumulation of nonsynonymous substitutions were associated with more precipitous declines in CD4+ cell numbers. In the V1V2 region, rates of accumulation of nonsynonymous substitutions were comparable with those in the C2V3 region, but similar rates were observed in AIDS-affected children and children with slow disease progression. The rate of accumulation of nonsynonymous substitutions in the pol region was lower than that in the C2V3 and V1V2 regions. Conclusions: Rates of accumulation of nucleotide substitutions vary across the HIV-1 genome and differ in relation to disease progression in children. The finding of greater rates of non-synonymous substitution in the immunodominant C2V3 region in children whose disease progressed rapidly is consistent with a vigorous but inadequate immune response in children who are unable to control HIV-1 infection.

AB - Objective: To compare patterns of nonsynonymous and synonymous substitutions over time in the V1V2 and C2V3 regions of human immunodeficiency virus type 1 (HIV-1) env and in a conserved segment of pol in HIV-1-infected children with varying rates of CD4+ T-cell decline. Study Design/Methods: Longitudinal study of HIV-1 genetic variants sampled from peripheral blood of 3 children affected with acquired immunodeficiency syndrome (AIDS) and 4 children with slow disease progression. Nested polymerase chain reaction (PCR) was used to detect HIV-1 genetic material in plasma-derived virions and cellular DNA. Sequence variants were enumerated by screening cloned PCR products using heteroduplex mobility assay (HMA) or single-strand conformation polymorphism analysis (SSCP) and nucleotide sequencing. Frequencies of nonsynonymous and synonymous substitutions within sampling points and the accumulation rate of nucleotide substitutions over the period of observation were calculated. Results: In the C2V3 region, higher rates of accumulation of nonsynonymous substitutions were associated with more precipitous declines in CD4+ cell numbers. In the V1V2 region, rates of accumulation of nonsynonymous substitutions were comparable with those in the C2V3 region, but similar rates were observed in AIDS-affected children and children with slow disease progression. The rate of accumulation of nonsynonymous substitutions in the pol region was lower than that in the C2V3 and V1V2 regions. Conclusions: Rates of accumulation of nucleotide substitutions vary across the HIV-1 genome and differ in relation to disease progression in children. The finding of greater rates of non-synonymous substitution in the immunodominant C2V3 region in children whose disease progressed rapidly is consistent with a vigorous but inadequate immune response in children who are unable to control HIV-1 infection.

KW - Disease progression

KW - HIV-1

KW - Molecular evolution

KW - Pediatric HIV infection

UR - http://www.scopus.com/inward/record.url?scp=0032009638&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032009638&partnerID=8YFLogxK

M3 - Article

C2 - 10195246

AN - SCOPUS:0032009638

VL - 1

SP - 224

EP - 239

JO - Journal of Human Virology

JF - Journal of Human Virology

SN - 1090-9508

IS - 3

ER -