Search results for "Resistance mutation"
showing 4 items of 14 documents
Mode of selection and experimental evolution of antiviral drugs resistance in vesicular stomatitis virus
2004
Abstract The possession of an antiviral resistance mutation benefits a virus when the corresponding antiviral is present. But does the resistant virus pay a fitness cost when the antiviral is absent? Would an evolutionary history of association between a genotype and a resistance mutation overcome this cost by changes compensating the harmful side-effect of resistance mutations? Are combined therapies more effective against the rise of resistant viruses or against evolutionary compensations? To explore all these questions, we took an experimental evolution approach. After selecting vesicular stomatitis virus (VSV) populations able to replicate under increasing concentrations of ribavirin an…
Delayed lysis confers resistance to the nucleoside analogue 5-fluorouracil and alleviates mutation accumulation in the single-stranded DNA bacterioph…
2014
ABSTRACT Rates of spontaneous mutation determine viral fitness and adaptability. In RNA viruses, treatment with mutagenic nucleoside analogues selects for polymerase variants with increased fidelity, showing that viral mutation rates can be adjusted in response to imposed selective pressures. However, this type of resistance is not possible in viruses that do not encode their own polymerases, such as single-stranded DNA viruses. We previously showed that serial passaging of bacteriophage ϕX174 in the presence of the nucleoside analogue 5-fluorouracil (5-FU) favored substitutions in the lysis protein E (P. Domingo-Calap, M. Pereira-Gomez, and R. Sanjuán, J. Virol. 86: 9640–9646, 2012, doi:10…
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…
Molecular epidemiology of HIV-1 subtype B in the Basque Country (Spain)
2012
The goal of this work was to study the HIV-1 subtype B epidemic in the Basque Country (Spain). For this, we used HIV samples submitted for genotypic testing of anti-retroviral resistance mutations from 2005 until 2008. Consequently, 2115 HIV-1 sequences comprising protease and retrotranscriptase (PR/RT) coding regions were analyzed. HIV transmission groups were identified by phylogenetic analysis. The 10 largest such groups were subsequently subjected to Bayesian phylogenetic and coalescent reconstructions, using a relaxed molecular clock model. The results obtained show that these groups have been long-standing: most of them were originated in the late 70s or early 80s, and none after the …