Slower evolution of human immunodeficiency virus type 1 quasispecies during progression to AIDS.

Abstract

The evolution of human immunodeficiency virus type 1 (HIV-1) quasispecies at the envelope gene was studied from the time of infection in 11 men who experienced different rates of CD4+ cell count decline and 6 men with unknown dates of infection by using DNA heteroduplex mobility assays. Quasispecies were genetically homogeneous near the time of seroconversion. Subsequently, slower proviral genetic diversification and higher plasma viremia correlated with rapid CD4+ cell count decline. Except for the fastest progressors to AIDS, highly diverse quasispecies developed in all subjects within 3 to 4 years. High quasispecies diversity was then maintained for years until again becoming more homogeneous in a subset of late-stage AIDS patients. Individuals who maintained high CD4+ cell counts showed continuous genetic turnover of their complex proviral quasispecies, while more closely related sets of variants were found in longitudinal samples of severely immunocompromised patients. The limited number of variants that grew out in short-term PBMC cocultures were rare in the uncultured proviral quasispecies of healthy, long-term infected individuals but more common in vivo in patients with low CD4+ cell counts. The slower evolution of HIV-1 observed during rapid progression to AIDS and in advanced patients may reflect ineffective host-mediated selection pressures on replicating quasispecies.

• Authors: E L Delwart, H Pan, H W Sheppard, D Wolpert, A U Neumann, B Korber, J I Mullins
• Journal: Journal of virology (J Virol) Vol. 71 Issue 10 Pg. 7498-508 (Oct 1997) ISSN: 0022-538X [Print] United States
• PMID: 9311829 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• DNA, Viral
• Nucleic Acid Heteroduplexes

Topics

• Acquired Immunodeficiency Syndrome (immunology, virology)
• CD4 Lymphocyte Count
• DNA, Viral (analysis)
• Disease Progression
• Evolution, Molecular
• Genes, env
• Giant Cells
• HIV Seropositivity (immunology, virology)
• HIV-1 (classification, genetics, isolation & purification)
• Humans
• Lymphocytes (immunology, virology)
• Male
• Nucleic Acid Heteroduplexes (analysis)
• Phenotype
• Phylogeny
• Polymerase Chain Reaction
• Time Factors
• Viremia (immunology)