Variation in RNA Virus Mutation Rates across Host Cells

Abstract

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 in baby hamster kidney, murine embryonic fibroblasts, colon cancer, and neuroblastoma cells (approx. 10−5 s/n/r). Cell immortalization through p53 inactivation and oxygen levels (1–21%) did not have a significant impact on viral replication fidelity. This shows that previously published mutation rates can be considered reliable despite being based on a narrow and artificial set of laboratory conditions. Interestingly, we also found that VSV mutated approximately four times more slowly in various insect cells compared with mammalian cells. This may contribute to explaining the relatively slow evolution of VSV and other arthropod-borne viruses in nature.

Molecular variability of Apple chlorotic leaf spot virus isolated in Belarus

“…High genetic diversity of RNA viruses was found to result from high frequency of spontaneous mutations (10 -6 to 10 -4 substitutions per nucleotide per genome copy) (Combe, Sanjuan 2014). Therefore, the population of RNA viruses can exist as a mixture of various mutant genotypes (Doningo 2002).…”

Tools to study pathogen-host interactions in bats

“…Because propagation of viruses in cell lines can select for members of the virus population that replicate most efficiently in the chosen cell type, the choice of cell line should be taken into consideration. Propagation of viruses in cell lines other than those of the natural host may lead to accumulation of adaptive mutations or attenuate the virus (Combe and Sanjuan, 2014), which in turn has implications for assessing host-pathogen interactions either in vivo or in vitro. For example, although wild type Marburg virus causes no disease in mice, it can be adapted to mice by serial passage to cause lethal disease (Qiu et al, 2014).…”

Structural-Statistical Properties of the Flavivirus Genomes

“…Кроме того, в CDSs генома флавивирусов наблюдается значительная доля однородных последовательностей. Возможно, это связано с высокой мутабильностью вируса [21], что может объяснять и другие особенности в отклонении от 3-профильности в CDSs вирусов (см. рис.…”