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

Freistadt, Marion S.; Vaccaro, Joseph A.; Eberle, Karen E.

doi:10.1186/1743-422x-4-44

Cited by 34 publications

(34 citation statements)

References 34 publications

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“…However, it must be noted that, nevertheless, the frequency of nonsense mutations is necessarily closer to the mutation rate than that of any other kind of nucleotide substitution. Like what has been previously established for other polymerases (18,21,34), the spontaneous mutation rate of HCV polymerase is biased toward transitions, and according to our data, the total mutation spectrum of HCV should be composed of two-thirds transitions and one-third transversions. Selection should alter this proportion because transitions are more often silent than transversions.…”

Section: Discussionsupporting

confidence: 87%

Effect of Ribavirin on the Mutation Rate and Spectrum of Hepatitis C Virus In Vivo

Cuevas

Gónzález-Candelas

Moya

et al. 2009

J Virol

146

130

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Their extremely error-prone replication makes RNA viruses targets for lethal mutagenesis. In the case of hepatitis C virus (HCV), the standard treatment includes ribavirin, a base analog with an in vitro mutagenic effect, but the in vivo mode of action of ribavirin remains poorly understood. Here, we test the mutagenic effects of ribavirin plus interferon treatment in vivo using a new method to estimate mutation rates based on the analysis of nonsense mutations. We apply this methodology to a large HCV sequence database containing over 15,000 reverse transcription-PCR molecular clone sequences from 74 patients infected with HCV. We obtained an estimate of the spontaneous mutation rate of ca. 10 ؊4 substitutions per site or lower, a value within the typically accepted range for RNA viruses. A roughly threefold increase in mutation rate and a significant shift in mutation spectrum were observed in samples from patients undergoing 6 months of interferon plus ribavirin treatment. This result is consistent with the known in vitro mutagenic effect of ribavirin and suggests that the antiviral effect of ribavirin plus interferon treatment is at least partly exerted through lethal mutagenesis.

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Section: Discussionsupporting

confidence: 87%

Effect of Ribavirin on the Mutation Rate and Spectrum of Hepatitis C Virus In Vivo

Cuevas

Gónzález-Candelas

Moya

et al. 2009

J Virol

146

130

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“…‡ See Dataset S4 for further details. error rate for the related poliovirus RdRp (32). In the FHVvirionRNAseq dataset, mutation frequency across the ORFs of the FHV genome is imbalanced with over twice the frequency of mutation at the third nucleotide position of each codon than at the first and second positions [as was also noticed for wild footand-mouth disease virus samples (1)].…”

Section: Resultsmentioning

confidence: 90%

Host RNAs, including transposons, are encapsidated by a eukaryotic single-stranded RNA virus

Routh

Domitrovic

Johnson

2012

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

106

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Next-generation sequencing is a valuable tool in our growing understanding of the genetic diversity of viral populations. Using this technology, we have investigated the RNA content of a purified nonenveloped single-stranded RNA virus, flock house virus (FHV). We have also investigated the RNA content of virus-like particles (VLPs) of FHV and the related Nudaurelia capensis omega virus. VLPs predominantly package ribosomal RNA and transcripts of their baculoviral expression vectors. In addition, we find that 5.3% of the packaged RNAs are transposable elements derived from the Sf21 genome. This observation may be important when considering the therapeutic use of VLPs. We find that authentic FHV virions also package a variety of host RNAs, accounting for 1% of the packaged nucleic acid. Significant quantities of host messenger RNAs, ribosomal RNA, noncoding RNAs, and transposable elements are readily detected. The packaging of these host RNAs elicits the possibility of horizontal gene transfer between eukaryotic hosts that share a viral pathogen. We conclude that the genetic content of nonenveloped RNA viruses is variable, not just by genome mutation, but also in the diversity of RNA transcripts that are packaged.deep-sequencing | virus evolution | virus assembly N ext-generation sequencing (NGS) is a powerful tool in the investigation of viral diversity from many different perspectives. NGS has been applied in directed approaches to investigate the prevalence of polymorphism or quasispecies present in a population of known viruses within a host, e.g., foot-and-mouth disease virus (1) or to follow the evolution of a viral genome and the frequency of known polymorphisms during the course of an infection, e.g., human rhinovirus (2) and HIV (3). The total genetic content of biological or clinical samples have been sequenced to uncover viruses present even at very low titers, for example, the presence of porcine circovirus-1 in Rotarix samples (4) and the identification of influenza virus subtypes and norovirus from nasopharyngeal and fecal samples collected during outbreaks (5).NGS has also been applied in unbiased approaches aimed at the discovery of new viral species without any advance genetic information. For example, the Merkel cell polyomavirus was discovered to be the causative agent of its eponymous carcinoma by deep sequencing the transcriptome of tumor cells and analyzing nonhost transcripts (6). Similarly, it has been possible to uncover the history of viral pathogens that have plagued an organism through the de novo assembly of the sequenced siRNAs that would have been generated to tackle viral infections. This approach has revealed the viral genomes of familiar miscreants as well as of new viruses, for example, in fruit flies, mosquitoes, and nematode worms (7).In this report, we employ NGS to investigate the total RNA encapsidated by authentic flock house virus (FHV) virions and by virus-like particles (VLPs) of FHV and of the related tetravirus, Nudaurelia capensis omega virus (NωV). Our analysis emplo...

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“…Positive strand RNA viruses replicate autonomously in the cytoplasm of the host cell and multiple genome copies (positive and negative forms) would be present. Furthermore, template switching, a recombination mechanism exhibited by positive strand RNA viruses, (Freistadt et al, 2007) may facilitate virus evolution possibly leading to species creation. Thus, co-occurrence of the S. invicta viruses within a host cell could lead to the evolution of new virus species by the template switching mechanism.…”

Section: Location Designationmentioning

confidence: 99%

Multiple virus infections occur in individual polygyne and monogyne Solenopsis invicta ants

Allen¹,

Valles²,

Strong³

2011

Journal of Invertebrate Pathology

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Concurrent infections of Solenopsis invicta colonies with S. invicta virus 1 (SINV-1), SINV-2, and SINV-3 has been reported. However, whether individual ants were capable of supporting multiple virus infections simultaneously was not known, nor whether the social form of the colony (polygyne or monogyne) had an influence on the occurrence of multiple infection rates in individual ants. S. invicta field populations were sampled sequentially to establish whether multiple virus infections co-occurred in individual worker ants. In addition, the intra-colony virus infection rates were compared in monogyne and polygyne field colonies to determine whether social form played a role in the viral infection prevalence. All combinations of virus infection (SINV-1, SINV-2, or SINV-3 alone, SINV-1 & SINV-2, SINV-1 & SINV-3, SINV-2 & SINV-3, and SINV-1, SINV-2 & SINV-3) were detected in individual worker ants as well as queens in the field. Thus, individual S. invicta ants can be infected simultaneously with all combinations of the S. invicta viruses. Colony social form did have an influence on the intra-colony prevalence of multiple S. invicta virus infections. Polygyne colonies exhibited significantly greater intra- and inter-colony single and multiple virus infections compared with monogyne colonies.

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

Cited by 34 publications

References 34 publications

Effect of Ribavirin on the Mutation Rate and Spectrum of Hepatitis C Virus In Vivo

Effect of Ribavirin on the Mutation Rate and Spectrum of Hepatitis C Virus In Vivo

Host RNAs, including transposons, are encapsidated by a eukaryotic single-stranded RNA virus

Multiple virus infections occur in individual polygyne and monogyne Solenopsis invicta ants

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