Variation in RNA virus mutation rates across host cells.
Variation in RNA virus mutation rates across host cells.
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DOI：
10.1371/journal.ppat.1003855
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发表时间：
2014-01
期刊：
影响因子：
6.7
通讯作者：
Sanjuán R
中科院分区：
文献类型：
--
作者：
Combe M;Sanjuán R
众所周知，RNA病毒比DNA病毒和微生物表现出更高的自发突变率。然而，它们的突变率变化很大，从每核苷酸每轮复制10−6到10−4个替换（s/n/r），这种变异性的原因仍然知之甚少。除了内在保真度或纠错能力的差异外，病毒突变率可能取决于宿主因素。在这里，我们评估了细胞环境对水疱性口炎病毒（VSV）自发突变率的影响，该病毒具有广泛的宿主范围和细胞亲和性。luria - delbr<e:1> ck波动试验和测序显示，VSV在幼鼠肾细胞、小鼠胚胎成纤维细胞、结肠癌和神经母细胞瘤细胞中发生相似的突变。10−5 s / n / r)。通过p53失活和氧气水平（1-21%）实现细胞永生对病毒复制保真度没有显著影响。这表明先前公布的突变率可以被认为是可靠的，尽管它是基于一组狭窄的人工实验室条件。有趣的是，我们还发现VSV在各种昆虫细胞中的突变速度大约是哺乳动物细胞的四倍。这可能有助于解释VSV和其他节肢动物传播的病毒在自然界中相对缓慢的进化。RNA病毒表现出很高的自发突变率，这一特征深刻地影响了病毒的进化、疾病的出现、耐药性的出现和疫苗的效力。然而，RNA病毒的突变率变化很大，决定这种变异性的因素仍然知之甚少。在这里，我们通过测量病毒在不同细胞类型和不同培养条件下的突变率来研究宿主因素对病毒复制保真度的影响。为了进行这些实验，我们选择了水泡性口炎病毒（VSV），这是一种昆虫传播的哺乳动物RNA病毒，具有非常广泛的细胞和宿主亲和性。我们发现VSV复制机制对由细胞永生化或温度和氧气水平变化驱动的细胞生理变化是稳健的。相比之下，VSV在昆虫细胞中的突变要比在哺乳动物细胞中的突变慢得多，这一发现可能有助于我们理解为什么节肢动物传播的病毒往往比自然界中直接传播的病毒进化得慢。
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. RNA viruses show high rates of spontaneous mutation, a feature that profoundly influences viral evolution, disease emergence, the appearance of drug resistances, and vaccine efficacy. However, RNA virus mutation rates vary substantially and the factors determining this variability remain poorly understood. Here, we investigated the effects of host factors on viral replication fidelity by measuring the viral mutation rate in different cell types and under various culturing conditions. To carry out these experiments we chose the vesicular stomatitis virus (VSV), an insect-transmitted mammalian RNA virus with an extremely wide cellular and host tropism. We found that the VSV replication machinery was robust to changes in cellular physiology driven by cell immortalization or shifts in temperature and oxygen levels. In contrast, VSV mutated significantly more slowly in insect cells than in mammalian cells, a finding may help us to understand why arthropod-borne viruses tend to evolve more slowly than directly transmitted viruses in nature.
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核武器自发突变的三个面：光谱，基因组复制模式和突变速率。
影响因子：
4.5
作者：
García-Villada L;Drake JW
通讯作者：
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影响因子：
64.5
作者：
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DOI：
10.1016/0005-2787(72)90425-x
发表时间：
1972-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
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作者：
BRAY, G;BRENT, TP
通讯作者：
BRENT, TP
DOI：
10.1126/science.1181766
发表时间：
2010-02-05
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
Ge P;Tsao J;Schein S;Green TJ;Luo M;Zhou ZH
通讯作者：
Zhou ZH