Kääriäinen L, Ranki M
Annu Rev Microbiol. 1984;38:91-109. doi: 10.1146/annurev.mi.38.100184.000515.
The studies with poliovirus have revealed that cells have a full capacity to translate uncapped mRNA, although their own mRNAs are capped and methylated. These observations have been confirmed by translation studies in fractionated systems in vitro. In poliovirus-infected cells, and in cell extracts prepared from them, a well-documented loss of capacity to translate capped mRNAs has been shown. This is due to the dissociation of cap-binding protein(s) from the initiation factor eIF-3. It has not been possible to show which virus-specific protein, if any, is responsible for this dissociation. It may be that once not used, the cap-binding protein is excluded passively from its normal association cycle with eIF-3, rendering the cells incapable of translating capped mRNAs. Late in reovirus infection a similar phenomenon is observed. The secondary transcription products of reovirus subviral particles are uncapped mRNAs, which are synthesized in abundance. Their capping and methylation is prevented in the SVPs due to a masking of the respective enzymes. The inability to translate capped mRNAs in lysates prepared from reovirus-infected cells, late in infection, may be due to a similar mechanism, as in poliovirus-infected cells. Simply, a large excess of uncapped mRNA competes with initiation factors without specific need for the cap-binding protein(s), which becomes dissociated from the eIF-3 and loses its activity. Inhibition of host protein synthesis, whether due to simple competition or specified by a viral gene product, leads apparently to a shortage of initiation factors and ribosomes, causing the cessation of translation of both capped and uncapped mRNA, and finally to cell death. The studies with UV-inactivated VSV, its temperature-sensitive mutants and defective-interfering LT-particles clearly suggest that inhibition of host-cell macromolecular synthesis can be induced by mechanisms that do not operate during normal VSV-infection. It may be that similar phenomena occur in guanidine-treated poliovirus-infected cells. In these cells the host protein synthesis is inhibited as a result of the translation of a few hundred incoming viral RNAs. It would be interesting to know whether the cap-binding protein is dissociated from initiation factors under these conditions. If not, another mechanism has to be revealed, which again may not be manifest during normal poliovirus infection. The inhibition of host RNA and DNA synthesized by various viruses has been less intensively studied than inhibition of protein synthesis. Apparently, good in vitro systems are needed to solve these difficult problems.
对脊髓灰质炎病毒的研究表明，尽管细胞自身的mRNA有帽结构并经过甲基化修饰，但细胞仍具有完全翻译无帽mRNA的能力。这些观察结果已通过体外分级分离系统中的翻译研究得到证实。在脊髓灰质炎病毒感染的细胞以及从中制备的细胞提取物中，已证实存在翻译有帽mRNA能力的明显丧失。这是由于帽结合蛋白与起始因子eIF-3解离所致。目前尚无法确定是哪种病毒特异性蛋白（如果有的话）导致了这种解离。可能是一旦不再被使用，帽结合蛋白就会被动地从其与eIF-3的正常结合循环中被排除，从而使细胞无法翻译有帽mRNA。在呼肠孤病毒感染后期也观察到类似现象。呼肠孤病毒亚病毒颗粒的二级转录产物是无帽mRNA，其大量合成。由于相关酶被掩盖，在亚病毒颗粒中它们的加帽和甲基化受到抑制。在感染后期从呼肠孤病毒感染的细胞制备的裂解物中无法翻译有帽mRNA，可能是由于与脊髓灰质炎病毒感染的细胞类似的机制。简单来说，大量过量的无帽mRNA与起始因子竞争，而无需帽结合蛋白，帽结合蛋白从eIF-3解离并失去活性。宿主蛋白合成的抑制，无论是由于简单的竞争还是由病毒基因产物指定，显然都会导致起始因子和核糖体短缺，导致有帽和无帽mRNA的翻译停止，最终导致细胞死亡。对紫外线灭活的水疱性口炎病毒（VSV）、其温度敏感突变体和缺陷干扰LT颗粒的研究清楚地表明，宿主细胞大分子合成的抑制可由正常VSV感染期间不发生作用的机制诱导。可能在胍处理的脊髓灰质炎病毒感染的细胞中也会出现类似现象。在这些细胞中，由于数百个进入的病毒RNA的翻译，宿主蛋白合成受到抑制。了解在这些条件下帽结合蛋白是否与起始因子解离将是很有趣的。如果没有，就必须揭示另一种机制，而这种机制在正常脊髓灰质炎病毒感染期间可能也不明显。与蛋白质合成抑制相比，各种病毒对宿主RNA和DNA合成的抑制研究较少。显然，需要良好的体外系统来解决这些难题。
