Search results for "Replication"
showing 10 items of 489 documents
Diminishing Returns of Population Size in the Rate of RNA Virus Adaptation
2000
ABSTRACT Whenever an asexual viral population evolves by adapting to new environmental conditions, beneficial mutations, the ultimate cause of adaptation, are randomly produced and then fixed in the population. The larger the population size and the higher the mutation rate, the more beneficial mutations can be produced per unit time. With the usually high mutation rate of RNA viruses and in a large enough population, several beneficial mutations could arise at the same time but in different genetic backgrounds, and if the virus is asexual, they will never be brought together through recombination. Thus, the best of these genotypes must outcompete each other on their way to fixation. This c…
Changes in protein domains outside the catalytic site of the bacteriophage Qβ replicase reduce the mutagenic effect of 5-azacytidine.
2014
ABSTRACT The high genetic heterogeneity and great adaptability of RNA viruses are ultimately caused by the low replication fidelity of their polymerases. However, single amino acid substitutions that modify replication fidelity can evolve in response to mutagenic treatments with nucleoside analogues. Here, we investigated how two independent mutants of the bacteriophage Qβ replicase (Thr210Ala and Tyr410His) reduce sensitivity to the nucleoside analogue 5-azacytidine (AZC). Despite being located outside the catalytic site, both mutants reduced the mutation frequency in the presence of the drug. However, they did not modify the type of AZC-induced substitutions, which was mediated mainly by …
Extremely high mutation rate of a hammerhead viroid
2009
Supporting information (Materials and methods, figs. S1-S3, suppl. references) available at: http://www.sciencemag.org/cgi/data/323/5919/1308/DC1/1
Variability in the mutation rates of RNA viruses
2014
ABSTRACT: It is well established that RNA viruses show extremely high mutation rates, but less attention has been paid to the fact that their mutation rates also vary strongly, from 10-6 to 10-4 substitutions per nucleotide per cell infection. The causes explaining this variability are still poorly understood, but candidate factors are the viral genome size and polarity, host-specific gene expression patterns, or the intracellular environment. Differences between animal and plant viruses, or between arthropod-borne and directly transmitted viruses have also been postulated. Finally, RNA viruses may be able to regulate the rate at which new mutations spread in the population by modifying f…
The cost of replication fidelity in human immunodeficiency virus type 1.
2006
Mutation rates should be governed by at least three evolutionary factors: the need for beneficial mutations, the benefit of minimizing the mutational load and the cost of replication fidelity. RNA viruses show high mutation rates compared with DNA micro-organisms, and recent findings suggest that the cost of fidelity might play a role in the evolution of increased mutation rates. Here, by analysing previously published data from HIV-1 reverse transcriptase in vitro assays, we show a trade-off between enzymatic accuracy and the maximum rate of polymerization, thus providing a biochemical basis for the fitness cost of fidelity in HIV-1. This trade-off seems to be related to inefficient exten…
Effect of Ribavirin on the Mutation Rate and Spectrum of Hepatitis C Virus In Vivo
2009
ABSTRACTTheir 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 ra…
Variation in RNA virus mutation rates across host cells.
2014
It is well established that RNA viruses exhibit higher rates of spontaneous mutation than DNA viruses and microorganisms. However, their mutation rates vary amply, from 10−6 to 10−4 substitutions per nucleotide per round of copying (s/n/r) and the causes of this variability remain poorly understood. In addition to differences in intrinsic fidelity or error correction capability, viral mutation rates may be dependent on host factors. Here, we assessed the effect of the cellular environment on the rate of spontaneous mutation of the vesicular stomatitis virus (VSV), which has a broad host range and cell tropism. Luria-Delbrück fluctuation tests and sequencing showed that VSV mutated similarly…
2-(2,6-Dihalophenyl)-3-(pyrimidin-2-yl)-1,3-thiazolidin-4-ones as non-nucleoside HIV-1 reverse transcriptase inhibitors.
2004
Several 1,3-thiazolidin-4-ones bearing a 2,6-dihalophenyl group at C-2 and a substituted pyrimidin-2-yl ring at the N-3 were synthesised and evaluated as anti-HIV agents. The results of the in vitro tests showed that some of them were highly effective inhibitors of human immunodeficiency virus type-1 (HIV-1) replication at 10–40 nM concentrations with minimal cytotoxicity. Structure–activity relationship studies revealed that the nature of the substituents at the 2 and 3 positions of the thiazolidinone nucleus had a significant impact on the in vitro anti-HIV activity of this class of potent antiretroviral agents. The compounds had significantly reduced activity against the characteristic N…
Risk factors and interventional strategies for BK polyomavirus infection after renal transplantation.
2012
BK virus (BKV)-induced viraemia after renal transplantation can be associated with severe impairment of graft function. This study evaluated possible risk factors for BKV replication and examined the outcomes following various currently used treatment approaches.Fifty-seven renal transplant recipients with BKV viraemia were retrospectively compared with 71 BKV-negative recipients to identify risk factors for BKV viraemia. Furthermore, outcome and graft function in 14 patients with BKV replication, in whom mycophenolate mofetil (MMF) was discontinued with a dose reduction of the remaining immunosuppressants, were compared with 32 patients in whom both MMF and the additional immunosuppressant…
Non-local multiscale approach for the impact of go or grow hypothesis on tumour-viruses interactions
2021
International audience; We propose and study computationally a novel non-local multiscale moving boundary mathematical model for tumour and oncolytic virus (OV) interactions when we consider the go or grow hypothesis for cancer dynamics. This spatio-temporal model focuses on two cancer cell phenotypes that can be infected with the OV or remain uninfected, and which can either move in response to the extracellular-matrix (ECM) density or proliferate. The interactions between cancer cells, those among cancer cells and ECM, and those among cells and OV occur at the macroscale. At the micro-scale, we focus on the interactions between cells and matrix degrading enzymes (MDEs) that impact the mov…