Lodish H F, Porter M
J Virol. 1981 May;38(2):504-17. doi: 10.1128/JVI.38.2.504-517.1981.
Infection of animal cells by vesicular stomatitis virus (VSV) results in inhibition of translation of cellular mRNA. We showed previously that, in BHK cells infected by the Glasgow isolate of VSV Indiana, this is due to competition during the initiation step of protein synthesis of viral and cellular mRNA for a constant, limiting number of ribosomes. We show here that infection of the same cells with the San Juan isolate of VSV resulted in a more rapid shutoff of host protein synthesis and that this was paralleled by a more rapid accumulation of viral mRNA. Extending our conclusion that shutoff is due to mRNA competition, we show further that the average size of polysomes translating viral and cellular mRNA was threefold smaller in cells infected by VSV San Juan than by VSV Glasgow, which, in turn, was about one-half that of uninfected cells. In all cases, cellular and viral mRNA's which encoded the same-sized polypeptides were found on the same-sized polysomes, a result indicating that the efficiency of translation of both types of mRNA's is about the same in the infected cell. Also, there was no preferential sequestration of viral or cellular mRNA's in ribonucleoprotein particles. Additional correlations between the levels of viral mRNA's and the inhibition of protein synthesis came from studies of three other wild-type VSV strains and also from studies with Vero and L cells. In particular, the rate of shutoff of L-cell protein synthesis after infection by any VSV isolate was slower than that in BHK cells, and this was correlated with a slower rate of accumulation of viral mRNA. VSV temperature-sensitive mutants which synthesized, at the nonper-missive temperature, no VSV mRNA failed to inhibit synthesis of cellular proteins. Stanners and co-workers (C. P. Stanners, A. M. Francoeur, and T. Lam, Cell 11:273-281, 1977) claimed that VSV mutant R1 inhibited synthesis of L cell protein synthesis less rapidly than did its parent wild-type strain HR. They concluded that this effect was due to a mutation in an unspecified VSV protein, "P." We found, in both L and BHK cells, that R1 infection resulted in a slightly slower inhibition of cellular mRNA translation than did HR infection and that this was correlated with a slightly reduced accumulation of VSV mRNA. The level of VSV mRNA, rather than any specific VSV protein, appeared to be the key factor in determining the rate of shutoff of host protein synthesis.
水泡性口炎病毒（VSV）感染动物细胞会导致细胞mRNA翻译受到抑制。我们之前表明，在被VSV印第安纳州格拉斯哥分离株感染的BHK细胞中，这是由于病毒和细胞mRNA在蛋白质合成起始步骤中竞争数量恒定且有限的核糖体所致。我们在此表明，用VSV圣胡安分离株感染相同细胞会导致宿主蛋白质合成更快地关闭，并且这与病毒mRNA更快地积累同时发生。扩展我们关于关闭是由于mRNA竞争的结论，我们进一步表明，在被VSV圣胡安感染的细胞中，翻译病毒和细胞mRNA的多核糖体平均大小比被VSV格拉斯哥感染的细胞小三倍，而后者又约为未感染细胞的一半。在所有情况下，编码相同大小多肽的细胞和病毒mRNA存在于相同大小的多核糖体上，这一结果表明在感染细胞中这两种类型mRNA的翻译效率大致相同。此外，在核糖核蛋白颗粒中不存在病毒或细胞mRNA的优先隔离。病毒mRNA水平与蛋白质合成抑制之间的其他相关性来自对其他三种野生型VSV毒株的研究以及对Vero和L细胞的研究。特别是，任何VSV分离株感染后L细胞蛋白质合成的关闭速率都比BHK细胞慢，并且这与病毒mRNA积累速率较慢相关。在非允许温度下不合成VSV mRNA的VSV温度敏感突变体无法抑制细胞蛋白质的合成。斯坦纳斯及其同事（C. P. 斯坦纳斯、A. M. 弗朗克尔和T. 林，《细胞》11:273 - 281, 1977）声称，VSV突变体R1抑制L细胞蛋白质合成的速度比其亲本野生型毒株HR慢。他们得出结论，这种效应是由于未指定的VSV蛋白“P”发生突变所致。我们发现，在L细胞和BHK细胞中，R1感染导致细胞mRNA翻译的抑制比HR感染略慢，并且这与VSV mRNA积累略有减少相关。VSV mRNA的水平而非任何特定的VSV蛋白似乎是决定宿主蛋白质合成关闭速率的关键因素。
