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Cited by 926HIV Research and TreatmentEvolution and Genetic DynamicsHIV/AIDS drug development and treatment

The DOI matches its Crossref record; 84 of the 84 references it cites were found in a registry or an index.

Consistent Viral Evolutionary Changes Associated with the Progression of Human Immunodeficiency Virus Type 1 Infection

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Shankarappa, Raj, Margolick, Joseph B., Gange, Stephen J., Rodrigo, Allen G., Upchurch, David, Farzadegan, Homayoon, Gupta, Phalguni, Rinaldo, Charles R., Learn, Gerald H., He, Xi, Huang, Xiao-Li, Mullins, James I.·1999·Journal of Virology
DOI 10.1128/jvi.73.12.10489-10502.1999PMC PMC113104
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Abstract

To understand the high variability of the asymptomatic interval between primary human immunodeficiency virus type 1 (HIV-1) infection and the development of AIDS, we studied the evolution of the C2-V5 region of the HIV-1 env gene and of T-cell subsets in nine men with a moderate or slow rate of disease progression. They were monitored from the time of seroconversion for a period of 6 to 12 years until the development of advanced disease in seven men. Based on the analysis of viral divergence from the founder strain, viral population diversity within sequential time points, and the outgrowth of viruses capable of utilizing the CXCR4 receptor (X4 viruses), the existence of three distinct phases within the asymptomatic interval is suggested: an early phase of variable duration during which linear increases (∼1% per year) in both divergence and diversity were observed; an intermediate phase lasting an average of 1.8 years, characterized by a continued increase in divergence but with stabilization or decline in diversity; and a late phase characterized by a slowdown or stabilization of divergence and continued stability or decline in diversity. X4 variants emerged around the time of the early- to intermediate-phase transition and then achieved peak representation and began a decline around the transition between the intermediate and late phases. The late-phase transition was also associated with failure of T-cell homeostasis (defined by a downward inflection in CD3+T cells) and decline of CD4+T cells to ≤200 cells/μl. The strength of these temporal associations between viral divergence and diversity, viral coreceptor specificity, and T-cell homeostasis and subset composition supports the concept that the phases described represent a consistent pattern of viral evolution during the course of HIV-1 infection in moderate progressors. Recognition of this pattern may help explain previous conflicting data on the relationship between viral evolution and disease progression and may provide a useful framework for evaluating immune damage and recovery in untreated and treated HIV-1 infections.

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Crossref · 10.1128/jvi.73.12.10489-10502.1999

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Research works printed but not linked: 3

  1. Kuiken C. L. Korber B. Epidemiological significance of intra- and inter-person variation of HIV-1.AIDS 8 1994 S73 S83
  2. Mantel N. The detection of disease clustering and a generalized regression approach.Cancer Res. 27 1967 209 220
  3. Pelletier E. Wain-Hobson S. AIDS is not caused by the extreme genetic variability of HIV.J. NIH Res. 8 1996 45 48

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Metadata

Authors
Shankarappa, R., Margolick, J. B., Gange, S. J., Rodrigo, A. G., Upchurch, D., Farzadegan, H., Gupta, P., Rinaldo, C. R., Learn, G. H., He, X., Huang, X.-L., & Mullins, J. I.
Affiliations
  • University of Washington (US)
  • <!--label omitted: 2-->Departments of Molecular Microbiology and Immunology2 and of
  • Johns Hopkins University (US)
  • University of Pittsburgh (US)
ORCID
Venue
Journal of Virology
Publisher
American Society for Microbiology
Published
1999-12
Volume
73
Issue
12
Pages
10489-10502
ISSN
  • 0022-538X (ISSN-L)
  • 1098-5514
DOI
10.1128/jvi.73.12.10489-10502.1999
PMC
PMC113104
OpenAlex
W2126515754
Cited by
926
References
84
Citations by year
2026: 7 · 2025: 12 · 2024: 14 · 2023: 19 · 2022: 16 · 2021: 13 · 2020: 22 · 2019: 33 · 2018: 24 · 2017: 33 · 2016: 31 · 2015: 35 · 2014: 36 · 2013: 50 · 2012: 57
FWCI
7.58
Type
journal article
Language
en
Open access
Licence
journals.asm.org/non-commercial-tdm-license (tdm)
Locations
  • Journal of Virology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01ai034783-05, 5r01ai032885-06)
  • National Institute of Allergy and Infectious Diseases (AI-34783, AI37984, U01AI035040, U01AI037984, U01AI035041, AI-32885, U01AI035039, U01AI035042, P30AI027757)
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
  • Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
Keywords
HIV-1, viral evolution, disease progression, asymptomatic HIV infection, HIV-1 env gene, viral divergence, viral population diversity, CXCR4, T cell homeostasis, CD4+ T cells, CD3+ T cells
MeSH terms
Base Sequence, DNA, Viral, Humans, Male, Molecular Sequence Data, Prospective Studies, HIV-1, HIV Infections, Gene Products, env, Disease Progression, Evolution, Molecular

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