Novella I S, Cilnis M, Elena S F, Kohn J, Moya A, Domingo E, Holland J J
Department of Biology, University of California, San Diego, La Jolla, 92093-0116, USA.
J Virol. 1996 Sep;70(9):6414-7. doi: 10.1128/JVI.70.9.6414-6417.1996.
Vesicular stomatitis virus (VSV) populations were repeatedly passaged in L-929 cells treated with alpha interferon (IFN-alpha) at levels of 25 U/ml. This IFN-alpha concentration induced a 99.9% inhibition of viral yield in standard infections. Analysis of viral fitness (overall replicative ability measured in direct competition with a reference wild-type VSV) after 21 passages in IFN-treated cells showed only a limited increase or no increase in fitness, compared with the greater increase upon parallel passage in cells not treated with IFN-alpha. However, this limited increase in fitness was more pronounced when competition assays were carried out with IFN-alpha-treated cells, suggesting the selection of VSV populations with a low level of resistance to IFN-alpha. Thus, despite the extensively documented capacity of VSV to adapt to changing environments, the antiviral state induced by IFN-alpha imposes adaptive constraints on VSV which are not readily overcome.
水泡性口炎病毒(VSV)群体在以25 U/ml的水平用α干扰素(IFN-α)处理的L-929细胞中反复传代。这种IFN-α浓度在标准感染中诱导了99.9%的病毒产量抑制。在IFN处理的细胞中传代21次后,对病毒适应性(与参考野生型VSV直接竞争测量的总体复制能力)的分析表明,与在未用IFN-α处理的细胞中平行传代时更大的增加相比,适应性仅有限增加或没有增加。然而,当用IFN-α处理的细胞进行竞争试验时,这种适应性的有限增加更为明显,这表明选择了对IFN-α具有低水平抗性的VSV群体。因此,尽管有大量文献记载VSV有适应不断变化的环境的能力,但IFN-α诱导的抗病毒状态对VSV施加了不易克服的适应性限制。