Unfinished Stories on Viral Quasispecies and Darwinian Views of Evolution

Más, Antonio; López-Galı́ndez, Cecilio; Cacho, Isabel; Gómez, Jordi; Martı́nez, Miguel Ángel

doi:10.1016/j.jmb.2010.02.005

Cited by 83 publications

(53 citation statements)

References 111 publications

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“…1 Although the historical perspective on quasispecies theory provided by Más et al serves as a valuable introduction to the subject, their article presents a polarized view of the applicability of quasispecies theory to RNA virus evolution and contains a number of important misunderstandings. 1 Herein, I present a counterargument: that for all its power as a theory, the data needed to demonstrate the existence of quasispecies in natural populations of RNA viruses are still lacking. Although elements of quasispecies theory have been debated for a number of years, 2,3 there is clearly still a major intellectual chasm between the proponents and opponents of quasispecies dynamics in RNA viruses.…”

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confidence: 99%

“…As noted by Más et al, this focus on the group rather than on the individual leads to the most interesting prediction of quasispecies theory: that populations with mutant distributions that do not differ greatly in fitness can sometimes outcompete those that contain mutants with a far wider range of fitness values, including some of very high individual fitness. 1 Such a phenomenon has been dubbed 'survival of the flattest' to distinguish it from the Darwinian notion of 'survival of the fittest' in which mutations of individual highest fitness are favored. 9 The survival of the flattest can also be thought of as a form of 'mutational robustness', that is, the maintenance of phenotype in the face of deleterious mutation pressure.…”

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confidence: 99%

“…13 Más et al discuss two other pieces of evidence that RNA viruses form quasispecies: that quasispecies theory provides the theoretical bedrock to antiviral therapy through 'lethal mutagenesis' and that quasispecies may be central to viral pathology. 1 Although there is no denying that quasispecies theory has been central to the development of treatment strategies based on the application of mutagens, 14,15 it is another matter to claim that the quasispecies explains lethal mutagenesis. This rests on the subtle, but essential, difference between generating an 'error catastrophe', which proponents of quasispecies theory claim to explain lethal mutagenesis, and breaching an 'extinction threshold', which may be a more realistic explanation and which does not rely on quasispecies dynamics.…”

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confidence: 99%

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The RNA Virus Quasispecies: Fact or Fiction?

Holmes

2010

Journal of Molecular Biology

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confidence: 99%

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The RNA Virus Quasispecies: Fact or Fiction?

Holmes

2010

Journal of Molecular Biology

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“…T he activities of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) and hepatitis C virus (HCV) RNA polymerase are not subject to error-correcting mechanisms, and as with other RNA viruses, replication of these viruses is highly error prone (1). The in vitro error rate of HCV polymerase has been estimated at ϳ10 Ϫ3 mutations per site for transitions and about 100-fold lower rates for transversions (2).…”

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confidence: 99%

“…Quasispecies diversity challenges host immune virus surveillance, antiviral therapies, and the development of effective vaccines (1). Of note, the genetic structure of viral quasispecies determines virus adaptability (11) and pathogenesis (12)(13)(14).…”

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confidence: 99%

Similarities between Human Immunodeficiency Virus Type 1 and Hepatitis C Virus Genetic and Phenotypic Protease Quasispecies Diversity

Martı́nez

Nevot

Jordan-Paiz

et al. 2015

J Virol

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Human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) are two highly variable RNA viruses that cause chronic infections in humans. Although HCV likely preceded the AIDS epidemic by some decades, the global spread of both viruses is a relatively recent event. Nevertheless, HCV global diversity is higher than that of HIV-1. To identify differences in mutant diversity, we compared the HIV-1 protease and HCV NS3 protease quasispecies. Three protease gene quasispecies samples per virus, isolated from a total of six infected patients, were genetically and phenotypically analyzed at high resolution (HIV-1, 308 individual clones; HCV, 299 clones). Single-nucleotide variant frequency did not differ between quasispecies from the two viruses (HIV-1, 2.4 ؋ 10 ؊3 ؎ 0.4 ؋ 10 ؊3 ; HCV, 2.1 ؋ 10 ؊3 ؎ 0.5 ؋ 10 ؊3 ) (P ‫؍‬ 0.1680). The proportion of synonymous substitutions to potential synonymous sites was similar (3.667 ؎ 0.6667 and 2.183 ؎ 0.9048, respectively) (P ‫؍‬ 0.2573), and Shannon's entropy values did not differ between HIV-1 and HCV (0.84 ؎ 0.02 and 0.83 ؎ 0.12, respectively) (P ‫؍‬ 0.9408). Of note, 65% (HIV-1) and 67% (HCV) of the analyzed enzymes displayed detectable protease activity, suggesting that both proteases have a similar mutational robustness. In both viruses, there was a rugged protease enzymatic activity landscape characterized by a sharp peak, representing the master sequence, surrounded by a collection of diverse variants present at lower frequencies. These results indicate that nucleotide quasispecies diversification during chronic infection is not responsible for the higher worldwide genetic diversity observed in HCV. IMPORTANCEHCV global diversity is higher than that of HIV-1. We asked whether HCV genetic diversification during infection is responsible for the higher worldwide genetic diversity observed in HCV. To this end, we analyzed and compared the genotype and enzymatic activities of HIV-1 and HCV protease quasispecies existing in infected individuals. Our results indicate that HIV-1 and HCV protease quasispecies have very similar genetic diversity and comparable rugged enzymatic activity landscapes. Therapy for HCV has expanded, with new therapeutic agents such as the direct-acting antivirals (DAAs). DAAs, which target HCV NS3 protease and other virus proteins, have improved cure rates. However, major questions remain to be elucidated regarding the virologic correlates of HCV eradication. The findings shown here may help our understanding of the different therapeutic responses observed during chronic HCV infection. T he activities of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) and hepatitis C virus (HCV) RNA polymerase are not subject to error-correcting mechanisms, and as with other RNA viruses, replication of these viruses is highly error prone (1). The in vitro error rate of HCV polymerase has been estimated at ϳ10 Ϫ3 mutations per site for transitions and about 100-fold lower rates for transversions (2). Slightly lower in vitro error ra...

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Animal Cell Technology

2021

Advanced Fermentation and Cell Technology

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Unfinished Stories on Viral Quasispecies and Darwinian Views of Evolution

Cited by 83 publications

References 111 publications

The RNA Virus Quasispecies: Fact or Fiction?

The RNA Virus Quasispecies: Fact or Fiction?

Similarities between Human Immunodeficiency Virus Type 1 and Hepatitis C Virus Genetic and Phenotypic Protease Quasispecies Diversity

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