Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
J Biol Chem. 2010 Dec 31;285(53):41604-13. doi: 10.1074/jbc.M110.176255. Epub 2010 Oct 26.
Mammalian reoviruses replicate in a broad range of hosts, cells, and tissues. These viruses display strain-dependent variation in tropism for different types of cells in vivo and ex vivo. Early steps in the reovirus life cycle, attachment, entry, and disassembly, have been identified as pivotal points of virus-cell interaction that determine the fate of infection, either productive or abortive. However, in studies of the differential capacity of reovirus strains type 1 Lang and type 3 Dearing to replicate in Madin-Darby canine kidney (MDCK) cells, we found that replication efficiency is regulated at a late point in the viral life cycle following primary transcription and translation. Results of genetic studies using recombinant virus strains show that reovirus tropism for MDCK cells is primarily regulated by replication protein μ2 and further influenced by the viral RNA-dependent RNA polymerase protein, λ3, depending on the viral genetic background. Furthermore, μ2 residue 347 is a critical determinant of replication efficiency in MDCK cells. These findings indicate that components of the reovirus replication complex are mediators of cell-selective viral replication capacity at a post-entry step. Thus, reovirus cell tropism may be determined at early and late points in the viral replication program.
哺乳动物呼肠孤病毒在广泛的宿主、细胞和组织中复制。这些病毒在体内和体外对不同类型的细胞的趋向性表现出与株有关的变化。呼肠孤病毒生命周期的早期步骤，包括附着、进入和拆卸，已被确定为病毒-细胞相互作用的关键点，决定了感染的命运，是有生产力的还是无生产力的。然而，在研究呼肠孤病毒 1 型 Lang 和 3 型 Dearing 株在 Madin-Darby 犬肾 (MDCK) 细胞中的复制能力的差异时，我们发现，在初级转录和翻译之后，复制效率在病毒生命周期的晚期受到调节。使用重组病毒株进行遗传研究的结果表明，呼肠孤病毒对 MDCK 细胞的趋向性主要由复制蛋白 μ2 调节，并且取决于病毒的遗传背景，进一步受到病毒 RNA 依赖性 RNA 聚合酶蛋白 λ3 的影响。此外，μ2 残基 347 是 MDCK 细胞中复制效率的关键决定因素。这些发现表明，呼肠孤病毒复制复合物的成分是在进入后步骤中介导细胞选择性病毒复制能力的介质。因此，呼肠孤病毒的细胞趋向性可能在病毒复制程序的早期和晚期确定。
