Population genetic estimation of the loss of genetic diversity during horizontal transmission of HIV-1

Edwards, Charles; Holmes, Edward C.; Wilson, Daniel J.; Viscidi, Raphael P.; Abrams, Elaine J.; Phillips, Rodney E.; Drummond, Alexei J.

doi:10.1186/1471-2148-6-28

Cited by 66 publications

(53 citation statements)

References 46 publications

(51 reference statements)

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“…The effective size of an intraindividual population of HIV-1 is only 10 3 or 10 4 , and HIV-1 transmission between individuals involves severe bottlenecks (20,21). Thus, allele substitutions within HIV-1 lineages must occur very rapidly and essentially independently of slow processes that affect the whole metapopulation of HIV-1.…”

Section: Discussionmentioning

confidence: 99%

“…Redundant multiple substitutions could be common in HIV-1 because of its low effective population size (21,22), so that the best substitution may not be the first one to get fixed, because of the temporary unavailability of the corresponding mutation. Clumping in pairs of successive nonsynonymous substitutions is approximately the same when the final amino acid can and cannot be reached through a single nonsynonymous substitution (Table 3).…”

Section: Discussionmentioning

confidence: 99%

“…HIV-1 must be prone to fixation of slightly deleterious mutations because of low effective population size and frequent bottlenecks (20,21). Indeed, amino acid reversals constitute almost half of all the pairs of successive nonsynonymous substitutions and thus make a large contribution to the observed clumping.…”

Section: Discussionmentioning

confidence: 99%

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Bursts of nonsynonymous substitutions in HIV-1 evolution reveal instances of positive selection at conservative protein sites

Bazykin

Dushoff

Levin

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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The fixation of a new allele can be driven by Darwinian positive selection or can be due to random genetic drift. Identifying instances of positive selection is a difficult task, because its impact is routinely obscured by the action of negative selection. The nature of the genetic code dictates that positive selection in favor of an amino acid replacement should often cause a burst of two or three nucleotide substitutions at a single codon site, because a large fraction of amino acid replacements cannot be achieved after just one nucleotide substitution. Here, we study pairs of successive nonsynonymous substitutions at one codon in the course of evolution of HIV-1 genes within HIV-1 populations inhabiting infected individuals. Such pairs are more numerous and more clumped than expected if different substitutions were independent and than what is observed for pairs of successive synonymous substitutions. Bursts of nonsynonymous substitutions in HIV-1 evolution cannot be explained by mutational biases and must, therefore, be due to positive selection. Both reversals, exact or imprecise, of fixed deleterious mutations and acquisitions of amino acids with new properties are responsible for the bursts. Temporal clumping is strongest at codon sites with a low overall rate of nonsynonymous evolution, implying that a substantial fraction of replacements of conservative amino acids are driven by positive selection. We identified many conservative sites of HIV-1 proteins that occasionally experience positive selection.clumping ͉ phylogeny ͉ reversals ͉ fitness landscape ͉ genetic code

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Bursts of nonsynonymous substitutions in HIV-1 evolution reveal instances of positive selection at conservative protein sites

Bazykin

Dushoff

Levin

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…Sequential bottlenecks are well known in population genetics to lead to the loss of even beneficial mutations (31,32). A population of two equally fit HCV replicon strains (e.g., Jc1/⌬ GFP and Jc1/⌬ mCherry ) within one cell can be considered to be a haploid asexual population with a neutral difference at one locus.…”

Section: Discussionmentioning

confidence: 99%

Rapid Intracellular Competition between Hepatitis C Viral Genomes as a Result of Mitosis

Webster¹,

Wissing²,

Herker³

et al. 2013

J Virol

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). This process, termed superinfection exclusion, does not involve downregulation of surface viral receptors but instead occurs inside the cell at the level of RNA replication. The originally infecting virus may occupy replication niches or sequester host factors necessary for viral growth, preventing effective growth of viruses that enter the cell later. However, there appears to be an additional level of intracellular competition between viral genomes that occurs at or shortly following mitosis. In the setting of cellular division, when two viral replicons of equivalent fitness are present within a cell, each has an equal opportunity to exclude the other. In a population of dividing cells, the competition between viral genomes proceeds apace, randomly clearing one or the other genome from cells in the span of 9 to 12 days. These findings demonstrate a new mechanism of intracellular competition between HCV strains, which may act to further limit HCV's genetic diversity and ability to recombine in vivo. Hepatitis C virus (HCV) is a positive-stranded, enveloped single-stranded RNA (ssRNA) virus in the Flavivirus family. Currently, HCV infects more than 180 million people worldwide, and the associated morbidity and mortality are second only to those caused by HIV among emerging infections (1). HCV is primarily transmitted parenterally, but vertical and sexual transmission may also occur. After acute infection, approximately 25% of patients spontaneously clear the virus. The remaining patients are chronically infected and may go on to develop hepatic steatosis, cirrhosis, and hepatocellular carcinoma (2).Complete in vitro replication of an HCV molecular clone was first demonstrated in 2005, using the genotype 2a virus JFH-1 (3-5). This clone, isolated from a Japanese male patient with fulminant hepatitis (6), replicated robustly in Huh7 cells and produced infectious virions in the absence of cell culture adaptive mutations. The availability of this infectious molecular clone provided a powerful experimental model with many advantages over the previously described HCV replicons (7). More recently, other groups have constructed highly infectious intergenotypic chimeras of JFH-1 and other HCV strains by making substitutions in the region from core to a portion of NS2 (8-10). The genotype 2a/2a chimera Jc1 is especially infectious (10).HCV blocks infection by other incoming HCV virions through a process known as superinfection exclusion (11,12). This process appears to occur after the virus enters the cell, which is different from the superinfection exclusion mechanism found in many other viral systems in which downregulation of cell surface viral receptors is involved. The intracellular superinfection block during HCV infection might result from competition between the primary and secondary viruses involving sequestration of key host factor(s) needed for viral replication or through occupancy of replicative niches on the endoplasmic reticulum (ER) membrane.Superinfection exclusion has clear implications for treating H...

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“…The high level of genetic diversity has important implications in screening, diagnostic testing, disease monitoring and treatment outcomes [6][7][8][9][10][11][12][13][14]. Questions have been raised on whether diversity may also affect viral transmissibility and pathogenicity [15][16][17][18][19][20]. Sadly, genetic diversity has been the major impediment in the effective vaccine design and development since the human immune response to HIV is strain-specific [21].…”

Section: Hiv-1 Genetic Diversitymentioning

confidence: 99%

HIV Diversity and Classification, Role in Transmission

Duri¹,

Stray‐Pedersen²,

Müller³

2013

AID

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The hallmark of HIV-1 is its extensive genetic diversity that emanates mainly from high mutations. Phylogenetically, HIV can be classified into geographically confined groups, types, subtypes and circulating recombinant forms (CRFs) that are however subject to change over time. HIV genetic diversity may partially explain the observed heterogeneity in HIV prevalence and has also been reported to impact on viral transmissibility and differential rates of disease progression. The aim of this review is to present a simple overview of the principles and concepts of HIV diversity and classification. Tracking the presence of new HIV strains is not only important for surveillance purposes but is also critical in facilitating personalized targeted therapy as well as forming the basis for development of the much anticipated effective vaccines against this scourge.

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Population genetic estimation of the loss of genetic diversity during horizontal transmission of HIV-1

Cited by 66 publications

References 46 publications

Bursts of nonsynonymous substitutions in HIV-1 evolution reveal instances of positive selection at conservative protein sites

Bursts of nonsynonymous substitutions in HIV-1 evolution reveal instances of positive selection at conservative protein sites

Rapid Intracellular Competition between Hepatitis C Viral Genomes as a Result of Mitosis

HIV Diversity and Classification, Role in Transmission

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