Permissive Replication of Homologous Murine Rotavirus in the Mouse Intestine Is Primarily Regulated by VP4 and NSP1
Permissive Replication of Homologous Murine Rotavirus in the Mouse Intestine Is Primarily Regulated by VP4 and NSP1
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DOI：
10.1128/jvi.00619-13
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发表时间：
2013-08-01
影响因子：
5.4
通讯作者：
Greenberg, Harry B.
中科院分区：
文献类型：
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作者：
Feng, Ningguo;Yasukawa, Linda L.;Greenberg, Harry B.
一般来说，同源轮状病毒(RV)比异源轮状病毒在同源宿主的肠道中更强，复制效率更高。RV宿主范围限制的遗传基础尚不完全清楚，可能是多基因的。在以前的研究中，编码VP3、VP4、VP7、非结构蛋白1(NSP1)和NSP4的RV基因都与菌株和宿主物种特异性感染有关。这些研究使用了不同的RV毒株、不同的宿主范围和不同的动物宿主，对于宿主范围限制的决定因素没有明确的共识。我们使用小鼠模型来证明，小鼠轮状病毒EW在哺乳小鼠的肠道复制是猴轮状病毒(RRV)的1,000到10,000倍。利用一系列EW x RRV重组体的肠道复制来鉴定影响RV在肠道复制的几个RV基因。VP4(由基因4编码)在肠道感染中的作用是菌株特异性的。轮状病毒VP4只略微降低了小鼠轮状病毒的感染性；然而，来自牛RV株(UK)的表达VP4的重组体严重限制了乳鼠的肠道复制。同源小鼠EW NSP1(由基因5编码)是促进高效肠道生长所必需的，但不是充分的。有效的肠道复制需要一系列编码VP3、NSP2和NSP3以及NSP1的小鼠基因。
Homologous rotaviruses (RV) are, in general, more virulent and replicate more efficiently than heterologous RV in the intestine of the homologous host. The genetic basis for RV host range restriction is not fully understood and is likely to be multigenic. In previous studies, RV genes encoding VP3, VP4, VP7, nonstructural protein 1 (NSP1), and NSP4 have all been implicated in strain-and host species-specific infection. These studies used different RV strains, variable measurements of host range, and different animal hosts, and no clear consensus on the host range restriction determinants emerged. We used a murine model to demonstrate that enteric replication of murine RV EW is 1,000- to 10,000-fold greater than that of a simian rotavirus (RRV) in suckling mice. Intestinal replication of a series of EW x RRV reassortants was used to identify several RV genes that influenced RV replication in the intestine. The role of VP4 (encoded by gene 4) in enteric infection was strain specific. RRV VP4 reduced murine RV infectivity only slightly; however, a reassortant expressing VP4 from a bovine RV strain (UK) severely restricted intestinal replication in the suckling mice. The homologous murine EW NSP1 (encoded by gene 5) was necessary but not sufficient for promoting efficient enteric growth. Efficient enteric replication required a constellation of murine genes encoding VP3, NSP2, and NSP3 along with NSP1.