Human Immunodeficiency Virus Type 1 Evolution In Vivo tracked by DNA Heteroduplex Mobility Assays

Department of Microbiology and Immunology, Stanford University School of Medicine, California 94305-5402.
Journal of Virology (Impact Factor: 4.65). 11/1994; 68(10):6672-83.
Source: PubMed

ABSTRACT High mutation rates and strong selective pressures imposed on human immunodeficiency viruses in vivo result in the formation of pools of genetic variants known as quasispecies. DNA heteroduplex mobility and tracking analyses were used to monitor the generation of HIV sequence diversity, to estimate quasispecies complexity, and to assess the turnover of genetic variants to approach an understanding of the relationship between viral quasispecies evolution in vivo and disease progression. Proviral DNA pools were nearly homogeneous soon after sexual transmission. The emergence and clearance of individual variants then occurred at different rates in different individuals. High quasispecies complexity was found in long-term-infected, asymptomatic individuals, while rapid CD4+ cell decline and AIDS were often, but not always, associated with lower quasispecies complexity. Proviral genetic variation was often low following in vitro culture, because of the outgrowth of one or a few variants that often became more abundant only later as proviruses in peripheral blood mononuclear cells. These studies provide insight into the dynamics of human immunodeficiency virus sequence changes in vivo and illustrate the utility of heteroduplex analysis for the study of phenomena associated with rapid genetic changes.

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Available from: Eric Delwart, Aug 23, 2015
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    • "Pairwise genetic distance between clonal sequences within each sample was calculated using Mega applying the Kimura 2-Parameter (http://www.megasoftware.nex). The maximum pairwise distance in homoduplex-only samples was 1.4%, which is in complete concordance with an earlier publication on HMA describing the absence of heteroduplexes below a pairwise genetic difference of 1.4% (Delwart et al., 1994). It is likely that superinfections with heterologous HIV-1 strains exceed the pairwise distance threshold for generating heteroduplexes of 1.4%. "
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