HIV evolutionary dynamics within and among hosts

Department of Zoology, University of Oxford, Oxford, UK.
AIDS reviews (Impact Factor: 3.79). 07/2006; 8(3):125-40.
Source: PubMed


The HIV evolutionary processes continuously unfold, leaving a measurable footprint in viral gene sequences. A variety of statistical models and inference techniques have been developed to reconstruct the HIV evolutionary history and to investigate the population genetic processes that shape viral diversity. Remarkably different population genetic forces are at work within and among hosts. Population-level HIV phylogenies are mainly shaped by selectively neutral epidemiologic processes, implying that genealogy-based population genetic inference can be useful to study the HIV epidemic history. Such evolutionary analyses have shed light on the origins of HIV, and on the epidemic spread of viral variants in different geographic locations and in different populations. The HIV genealogies reconstructed from within-host sequences indicate the action of selection pressure. In addition, recombination has a significant impact on HIV genetic diversity. Accurately quantifying both the adaptation rate and the population recombination rate of HIV will contribute to a better understanding of immune escape and drug resistance. Characterizing the impact of HIV transmission on viral genetic diversity will be a key factor in reconciling the different population genetic processes within and among hosts.

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Available from: Philippe Lemey
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    • "By sequencing multiple isolates from the same infected horses our analyses have, for the first time, shed light on the complex population dynamics of S. equi during carriage within the host. The observation of an increased substitution rate within persistent infection mirrors the situation in human immunodeficiency virus (HIV) infection where mutations accrue faster within hosts than at the epidemic level (Herbeck et al. 2006; Lemey et al. 2006). "
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    • "This results in generating a large number of variants (quasispecies) in a host and increasing genetic diversity in a viral population [20]. By analyzing the genetic relationships among quasispecies, the dynamic evolutional pathway of a variant can be tracked on a time scale within and among hosts [21,22]. In the early stage of viral replication, HIV variants with new point mutations account for only a small proportion of the total wild-type populations, thus a particular point mutation at an allele is detected as a mixture along with the wild-type by conventional population-based (Sanger) sequencing, which is termed as ambiguous mutation/nucleotide. "
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    • "This rapid diversification is driven by a low fidelity reverse transcriptase (2.5–3.4×10−5 mutations per site per generation), high replication rate (1010 virions produced daily), high recombination rate, genetic plasticity of viral proteins [7], and strong host immune selective pressures [3]. The proportions of sites that undergo substitutions differ both within and between HIV-1 coding regions and so studying how specific coding regions evolve provides important insight into HIV-1 pathogenesis and disease because [6], [8], [9]. "
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