Barrett John W, Shun Chang Chew, Wang Gen, Werden Steven J, Shao Zhuhong, Barrett Catherine, Gao Xiujuan, Belsito Tara A, Villenevue Danielle, McFadden Grant
The Biotherapeutics Research Group, Robarts Research Institute, The University of Western Ontario, London, Ontario, Canada N6G 2V4.
Virology. 2007 Apr 25;361(1):123-32. doi: 10.1016/j.virol.2006.11.015. Epub 2006 Dec 20.
The myxoma virus M063R gene product exhibits some sequence similarity to the poxvirus host range gene, C7L, of vaccinia virus. To address the potential host range function of the M063R gene product in rabbits, a deletion mutant of myxoma virus (vMyx63KO) was generated and characterized. vMyx63KO replicated to normal titre levels and produced foci that were indistinguishable from those produced by MV in vitro in a monkey kidney cell line (BGMK) that are permissive for wild type MV. However, vMyx63KO failed to replicate in all rabbit cell lines tested, including both primary and established cells lines, as well as cells derived from a variety of tissues. M063R expression was not required for myxoma virus binding, entry or early gene expression, whereas DNA replication was aborted and late genes were not expressed in vMyx63KO infected rabbit cells. Thus, the replication block for vMyx63KO in rabbit cells preceded the stage of late gene expression and DNA replication. Finally, an in vivo pathogenesis study indicated that vMyx63KO failed to cause any signs of classic myxomatosis in infected rabbits, but functioned as a non-replicating vaccine and provided protection for subsequent challenge by wild type myxoma virus. Altogether, these observations demonstrate that M063R plays a critical role in determining the host specificity of myxoma virus in rabbit cells.
黏液瘤病毒M063R基因产物与痘苗病毒的痘病毒宿主范围基因C7L表现出一些序列相似性。为了研究M063R基因产物在兔中的潜在宿主范围功能，构建并鉴定了黏液瘤病毒的缺失突变体（vMyx63KO）。vMyx63KO在体外猴肾细胞系（BGMK，对野生型黏液瘤病毒敏感）中复制至正常滴度水平，并产生与黏液瘤病毒产生的病灶无法区分的病灶。然而，vMyx63KO在所有测试的兔细胞系中均无法复制，包括原代细胞系和已建立的细胞系，以及来自多种组织的细胞。黏液瘤病毒的结合、进入或早期基因表达不需要M063R的表达，而在感染vMyx63KO的兔细胞中，DNA复制中止且晚期基因未表达。因此，vMyx63KO在兔细胞中的复制阻滞发生在晚期基因表达和DNA复制阶段之前。最后，一项体内发病机制研究表明，vMyx63KO在感染的兔中未能引起任何经典黏液瘤病的迹象，但作为一种非复制性疫苗发挥作用，并为随后野生型黏液瘤病毒的攻击提供保护。总之，这些观察结果表明，M063R在决定黏液瘤病毒在兔细胞中的宿主特异性方面起着关键作用。
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