RNA virus fitness

Domingo, Esteban; Menéndez‐Arias, Luis; Holland, John J.

doi:10.1002/(sici)1099-1654(199707)7:2<87::aid-rmv188>3.0.co;2-0

Cited by 115 publications

(24 citation statements)

References 67 publications

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“…Absence of exonucleolytic editing function in RdRPs is often cited as the reason for high sequence variation (quasi-species) of RNA viruses [1]. However, absence of an exonucleolytic editing activity does not account for high sequence variation of poliovirus, since the values measured here are much less error-prone than predicted.…”

Section: Discussionmentioning

confidence: 71%

“…These undesirable properties of RNA viruses are thought to be mediated by "quasi-species" phenomena. Recent theoretical and experimental work render quasi-species a useful framework by which we may understand RNA viruses [1]. In this model, an RNA virus population exists at its highest possible ("threshold") mutation rate, maximizing adaptability while ensuring population survival.…”

Section: Introductionmentioning

confidence: 99%

“…The RNA-dependent RNA polymerases (RdRPs) lack of exonucleolytic editing is often cited as the reason that RNA viruses have high sequence variation [1]. If so, one would expect sequence variation rates to resemble RdRP fidelity values.…”

Section: Introductionmentioning

confidence: 99%

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Biochemical characterization of the fidelity of poliovirus RNA-dependent RNA polymerase

Freistadt

Vaccaro

Eberle

2007

Virol J

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Background: Putative high mutation rates of RNA viruses are believed to mediate undesirable phenomena, such as emergence of drug resistance. However, very little is known about biochemical fidelity rates for viral RNA-dependent RNA polymerases. Using a recently developed in vitro polymerase assay for poliovirus polymerase 3D pol JBC 275:5329], we measured fidelity for each possible mismatch. Polymerase fidelity, in contrast to sequence error rate, is biochemically defined as k pol /K d of {(correct plus incorrect) divided by incorrect} incorporations, such that a larger value connotes higher fidelity.

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Section: Discussionmentioning

confidence: 71%

Section: Introductionmentioning

confidence: 99%

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Biochemical characterization of the fidelity of poliovirus RNA-dependent RNA polymerase

Freistadt

Vaccaro

Eberle

2007

Virol J

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“…As a result, each viral genome is likely to differ from every other virus by one or more point mutations. The complex populations thus generated, called quasispecies, have been hypothesized to be important for survival of the population as a whole in the presence of selective pressure, under which a few viruses that contain beneficial mutations would survive and act as founders for the next generation [1,4]. For example, viruses with mutations that confer resistance to neutralizing antibodies would benefit the virus population as a whole under selective pressure from the host immune response.…”

Section: Introductionmentioning

confidence: 99%

Increased Fidelity Reduces Poliovirus Fitness and Virulence under Selective Pressure in Mice

2005

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RNA viruses have high error rates, and the resulting quasispecies may aid survival of the virus population in the presence of selective pressure. Therefore, it has been theorized that RNA viruses require high error rates for survival, and that a virus with high fidelity would be less able to cope in complex environments. We previously isolated and characterized poliovirus with a mutation in the viral polymerase, 3D-G64S, which confers resistance to mutagenic nucleotide analogs via increased fidelity. The 3D-G64S virus was less pathogenic than wild-type virus in poliovirus-receptor transgenic mice, even though only slight growth defects were observed in tissue culture. To determine whether the high-fidelity phenotype of the 3D-G64S virus could decrease its fitness under a defined selective pressure, we compared growth of the 3D-G64S virus and 3D wild-type virus in the context of a revertible attenuating point mutation, 2C-F28S. Even with a 10-fold input advantage, the 3D-G64S virus was unable to compete with 3D wild-type virus in the context of the revertible attenuating mutation; however, in the context of a non-revertible version of the 2C-F28S attenuating mutation, 3D-G64S virus matched the replication of 3D wild-type virus. Therefore, the 3D-G64S high-fidelity phenotype reduced viral fitness under a defined selective pressure, making it likely that the reduced spread in murine tissue could be caused by the increased fidelity of the viral polymerase.

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“…Viral fitness can be defined as the summation of parameters that quantify the degree of virus adaptation to a given environment [6]. Virus replication is an error-prone process resulting in a large number of variants in patients.…”

Section: Definition Of Viral Fitness and Methods Of Analysismentioning

confidence: 99%

Fitness of neuraminidase inhibitor-resistant influenza A viruses

Baranovich

Webster

Govorkova

2011

Current Opinion in Virology

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Antiviral drugs are important components for the control of influenza. The key question is whether antiviral use or natural virus evolution will lead to the emergence of drug-resistant virus with comparable or superior fitness to drug-susceptible counterpart. Currently, neuraminidase (NA) inhibitors (NAIs) are the first choice for influenza prevention and treatment. In this article we will review complex process of the risk assessment for the fitness of NAIs-resistant seasonal H1N1 and H3N2, pandemic 2009 H1N1, and highly pathogenic H5N1 influenza A viruses: identification of antiviral susceptibility, degree of functional NA loss, molecular markers of resistance, and evaluation of replicative ability in vivo, virulence and transmissibility in animal studies (mouse, ferret and guinea pig models).

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RNA virus fitness

Cited by 115 publications

References 67 publications

Biochemical characterization of the fidelity of poliovirus RNA-dependent RNA polymerase

Biochemical characterization of the fidelity of poliovirus RNA-dependent RNA polymerase

Increased Fidelity Reduces Poliovirus Fitness and Virulence under Selective Pressure in Mice

Fitness of neuraminidase inhibitor-resistant influenza A viruses

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