Resistance of human immunodeficiency virus type 1 to protease inhibitors: selection of resistance mutations in the presence and absence of the drug

Borman, Andrew M.; Paulous, Sylvie; Clavel, François

doi:10.1099/0022-1317-77-3-419

Cited by 141 publications

(92 citation statements)

References 31 publications

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“…28 The minor mutations have no major effect on drug resistance by themselves, but if a major mutation occurs in the presence of minor mutations, resistance to PIs may be drastically increased. [29][30][31] To obtain an estimate of the probability of the future cooccurrence of major-minor mutations, we performed Shannon entropy analysis, which measures the probability of acquiring mutations in a given set of genomic sequences. 22 This analysis revealed that certain regions of protease gene sequences in our study cohort exhibited high entropy, indicating a higher probability of the later occurrence of mutations.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of Transmitted Drug Resistance Mutations in HIV-1-Infected Drug-Naive Patients from Urban and Suburban Regions of Kenya

Onsongo

Abidi

Khamadi³

et al. 2016

AIDS Research and Human Retroviruses

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Section: Discussionmentioning

confidence: 99%

Prevalence of Transmitted Drug Resistance Mutations in HIV-1-Infected Drug-Naive Patients from Urban and Suburban Regions of Kenya

Onsongo

Abidi

Khamadi³

et al. 2016

AIDS Research and Human Retroviruses

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“…1a). This model implies that: (i) whether a locus is in the wild-type or the mutant state or is compensating depends on the state of other loci; (ii) a sequence with maximum fitness 1 is not unique; (iii) the number of locus differences between a sequence and a best-fit sequence is, generally, not equal to k. The existence of compensatory mutations is well established experimentally for a number of viruses and bacteria (15,(32)(33)(34)(35)(36), although the degree of compensation is often not 100%. A compensatory mutation, for example, can restore the proper folding of a protein (or RNA) or the local binding between two protein (or RNA) regions impaired by a mutation at the first locus.…”

Section: The Multilocus Model Of Asexual Populationsmentioning

confidence: 99%

The solitary wave of asexual evolution

Rouzine

Wakeley

Coffin

2003

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

240

394

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Using a previously undescribed approach, we develop an analytic model that predicts whether an asexual population accumulates advantageous or deleterious mutations over time and the rate at which either process occurs. The model considers a large number of linked identical loci, or nucleotide sites; assumes that the selection coefficient per site is much less than the mutation rate per genome; and includes back and compensating mutations. Using analysis and Monte Carlo simulations, we demonstrate the accuracy of our results over almost the entire range of population sizes. Two limiting cases of our results, when either deleterious or advantageous mutations can be neglected, correspond to the Fisher-Muller effect and Muller's ratchet, respectively. By comparing predictions of our model (no recombination) to those of simple single-locus models (strong recombination), we show that the accumulation of advantageous mutations is slowed by linkage over a broad, finite range of population size. This supports the view of Fisher and Muller, who argued in the 1930s that progressive evolution of organisms is slowed because loci at which beneficial mutations can occur are often linked together on the same chromosome. These results follow from our main finding, that distribution of sequences over the mutation number evolves as a traveling wave whose speed and width depend on population size and other parameters. The model explains a logarithmic dependence of steady-state fitness on the population size reported recently for an RNA virus. T he scope of evolutionary biology ranges from understanding the origin and extinction of species to predicting the accumulation of drug-or antibody-resistant mutations in a population of microbes during an infection of an individual. Viruses like HIV in which persistent infection of individuals lasts for large numbers of viral generations provide a valuable opportunity to test evolutionary theory by comparing model predictions to a wealth of readily obtained data. In addition, evolutionary models can be used to infer important properties of viral populations.The forces that produce and maintain genetic variation in a population are thought to be known. These include the ''systematic pressures'' (1) of mutation, natural selection, and migration. If these were the only forces operating, the fate of the population could be modeled deterministically. However, all evolution occurs in finite-size populations, which is the source of the other major evolutionary factor: random genetic drift. Drift adds a stochastic element to evolution, resulting from the chance sampling of individuals from one generation to the next and from the fact that not all possible genetic variants can be present in a finite population. For given levels of systematic pressure, evolution will be mostly deterministic if the population size is large enough but will be mostly neutral and dominated by drift (2) when the population size is small. Between these two limits there exists a large intermediate region, in which both selec...

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“…Parallel evolution is a special case of convergent evolution, which describes a substitution to the same nucleotide that is present in another, independently evolved lineage. Parallel and convergent molecular evolution have been observed in both experimental populations Crill et al 2000;Cunningham et al 1997;Treves et al 1998;Wichman et al 1999) and natural populations (Borman et al 1996;¡rench-Constant 1994;Stewart & Wilson 1987) of viruses, bacteria and even insects and mammals exposed to the same, strong selection pressures.…”

Section: Introductionmentioning

confidence: 99%

Experimental evolution recapitulates natural evolution

Wichman

Scott

Yarber

et al. 2000

Phil. Trans. R. Soc. Lond. B

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Genomes of the closely related bacteriophages fX174 and S13 are 5386 bases long and di¡er at 114 nucleotides, a¡ecting 28 amino acids. Both parental phages were adapted to laboratory culture conditions in replicate lineages and analysed for nucleotide changes that accumulated experimentally. Of the 126 experimental substitutions, 90% encoded amino-acid changes, and 62% of the substitutions occurred in parallel in more than one exp erimental line. Furthermore, missense changes at 12 of the experimental sites were at residues di¡ering between the parental phages; in ten cases the fX174 experimental lineages were convergent with the S13 parent, or vice versa, at both the nucleotide and amino-acid levels. Convergence at a site was even obtained in both directions in three cases. These results point to a limited number of pathways taken during evolution in these viruses, and also raise the possibility that much of the amino-acid variation in the natural evolution of these viruses has been selected.

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Resistance of human immunodeficiency virus type 1 to protease inhibitors: selection of resistance mutations in the presence and absence of the drug

Cited by 141 publications

References 31 publications

Prevalence of Transmitted Drug Resistance Mutations in HIV-1-Infected Drug-Naive Patients from Urban and Suburban Regions of Kenya

Prevalence of Transmitted Drug Resistance Mutations in HIV-1-Infected Drug-Naive Patients from Urban and Suburban Regions of Kenya

The solitary wave of asexual evolution

Experimental evolution recapitulates natural evolution

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