The error threshold

Biebricher, Christof Κ.; Eigen, Manfred

doi:10.1016/j.virusres.2004.11.002

Cited by 180 publications

(179 citation statements)

References 45 publications

Supporting

Mentioning

175

Contrasting

Order By: Relevance

“…One such strategy, termed lethal mutagenesis, is based on the theoretical concept of entry into error catastrophe (Eigen, 1971;Eigen et al, 1988;Eigen & Schuster, 1979). According to this concept, for any replicating entity, there is an upper value of the mutation rate, termed the error threshold, which must not be crossed if the wild-type genome distribution is to be kept stable (Biebricher & Eigen, 2005;Eigen, 2002). Applied to viruses, an increase of the mutation rate above some critical value might lead to drift of sequences, disorganization of the quasispecies and, consequently, to loss of infectivity (Eigen, 2002).…”

Section: Introductionmentioning

confidence: 99%

An interfering activity against lymphocytic choriomeningitis virus replication associated with enhanced mutagenesis

Martı́n

Abia

Domingo

et al. 2009

Journal of General Virology

View full text Add to dashboard Cite

Previous studies have documented that, in the presence of the mutagenic base analogue 5-fluorouracil (FU), lymphocytic choriomeningitis virus (LCMV) that persisted in BHK-21 cells decreased its infectivity to a larger extent than intracellular viral RNA levels, prior to virus extinction. This observation, together with in silico simulations, led to the proposal of the lethal defection model of virus extinction. This model suggests the participation of defective-interfering genomes in the loss of infectivity by increased mutagenesis. Since LCMV naturally produces defective-interfering particles, it was important to show that a capacity to interfere is produced in association with FU treatment. Here, we document that BHK-21 cells persistently infected with LCMV grown in the presence of FU, but not in its absence, generated an interfering activity that suppressed LCMV infectivity. Interference was specific for LCMV and was sensitive to UV irradiation and its activity was dose-and time-dependent. The interfering preparations produced positive LCMV immunofluorescence and viral particles seen by electron microscopy when used to infect cells, despite some preparations being devoid of detectable infectivity. Interference did not involve significant increases of mutant spectrum complexity, as predicted by the lethal defection model. The results provide support for a specific interference associated with LCMV when the virus replicates in the presence of FU. The excess of interference relative to that observed in the absence of FU is necessary for LCMV extinction.

show abstract

Section: Introductionmentioning

confidence: 99%

An interfering activity against lymphocytic choriomeningitis virus replication associated with enhanced mutagenesis

Martı́n

Abia

Domingo

et al. 2009

Journal of General Virology

View full text Add to dashboard Cite

show abstract

“…D s 13 is from S. lycopersicum 'Heinz 1706' plants infected with PSTVd variants QFA (mild, GenBank AC U23059.1), C3 (severe, HE575349.1), or AS1 ("lethal," AY518939.1). Plants containing 3 true leaves were biolistically inoculated 42 with StyI-cleaved full-length cloned cDNA, 41 and plants were maintained in climate boxes at 28 C under a mixture of fluorescent and incandescent illumination (10,000 lx for a 16 h-day period). Samples of leaf and stem tissue were collected 30 d post infection (dpi); total RNA was prepared by phenol/chloroform extraction and ethanol precipitation, and small RNAs were enriched by denaturing gel-electrophoresis and gelelution.…”

Section: Deep-sequencing Data Sets Of Small Rnasmentioning

confidence: 99%

“…These landscapes reflect a combination of replication efficiency, selection, and sequencing errors. We evaluated the viroids' sequence space from the deep-sequencing data following methods established for RNA viruses [23][24][25][26][27] and applied the quasispecies theorem 6,28 and associated concepts to viroids to estimate a lower bound for the replication fidelity of their genomes.…”

Section: Introductionmentioning

confidence: 99%

Viroid quasispecies revealed by deep sequencing

et al. 2017

View full text Add to dashboard Cite

Viroids are non-coding single-stranded circular RNA molecules that replicate autonomously in infected host plants causing mild to lethal symptoms. Their genomes contain about 250-400 nucleotides, depending on viroid species. Members of the family Pospiviroidae, like the Potato spindle tuber viroid (PSTVd), replicate via an asymmetric rolling-circle mechanism using the host DNA-dependent RNA-Polymerase II in the nucleus, while members of Avsunviroidae are replicated in a symmetric rolling-circle mechanism probably by the nuclear-encoded polymerase in chloroplasts. Viroids induce the production of viroid-specific small RNAs (vsRNA) that can direct (post-)transcriptional gene silencing against host transcripts or genomic sequences. Here, we used deep-sequencing to analyze vsRNAs from plants infected with different PSTVd variants to elucidate the PSTVd quasipecies evolved during infection. We recovered several novel as well as previously known PSTVd variants that were obviously competent in replication and identified common strand-specific mutations. The calculated mean error rate per nucleotide position was less than 5 £ 10 ¡ 3 , quite comparable to the value of 2:5 £ 10 ¡ 3 reported for a member of Avsunviroidae. The resulting error threshold allows the synthesis of longer-than-unit-length replication intermediates as required by the asymmetric rolling-circle mechanism of members of Pospiviroidae.

show abstract

“…The mathematical quasispecies theory [8][9][10][11] describes populations of replicons as a collection of a master genomes and a diverse cloud of mutants, which all together contribute to the phenotypic properties of the entire population. Under this view, the entire quasispecies, rather than individuals, is the target of natural selection [12,13]. A remarkable result of the quasispecies theory is the prediction of the existence of a phase transition at a critical mutation rate, μ c , the error-threshold, beyond which the master sequence is lost and the quasispecies is dominated by the mutant genomes.…”

Section: Introductionmentioning

confidence: 99%