Reovirus nonstructural protein σ1s is required for the establishment of viremia and hematogenous viral dissemination. However, the function of σ1s during the reovirus replication cycle is not known. In this study, we found that σ1s was required for efficient reovirus replication in simian virus 40 (SV40)-immortalized endothelial cells (SVECs), mouse embryonic fibroblasts, human umbilical vein endothelial cells (HUVECs), and T84 human colonic epithelial cells. In each of these cell lines, wild-type reovirus produced substantially higher viral titers than a σ1s-deficient mutant. The σ1s protein was not required for early events in reovirus infection, as evidenced by the fact that no difference in infectivity between the wild-type and σ1s-null viruses was observed. However, the wild-type virus produced markedly higher viral protein levels than the σ1s-deficient strain. The disparity in viral replication did not result from differences in viral transcription or protein stability. We further found that the σ1s protein was dispensable for cell killing and the induction of type I interferon responses. In the absence of σ1s, viral factory (VF) maturation was impaired but sufficient to support low levels of reovirus replication. Together, our results indicate that σ1s is not absolutely essential for viral protein production but rather potentiates reovirus protein expression to facilitate reovirus replication. Our findings suggest that σ1s enables hematogenous reovirus dissemination by promoting efficient viral protein synthesis, and thereby reovirus replication, in cells that are required for reovirus spread to the blood.

IMPORTANCE Hematogenous dissemination is a critical step in the pathogenesis of many viruses. For reovirus, nonstructural protein σ1s is required for viral spread via the blood. However, the mechanism by which σ1s promotes reovirus dissemination is unknown. In this study, we identified σ1s as a viral mediator of reovirus protein expression. We found several cultured cell lines in which σ1s is required for efficient reovirus replication. In these cells, wild-type virus produced substantially higher levels of viral protein than a σ1s-deficient mutant. The σ1s protein was not required for viral mRNA transcription or viral protein stability. Since reduced levels of viral protein were synthesized in the absence of σ1s, the maturation of viral factories was impaired, and significantly fewer viral progeny were produced. Taken together, our findings indicate that σ1s is required for optimal reovirus protein production, and thereby viral replication, in cells required for hematogenous reovirus dissemination.

呼肠孤病毒非结构蛋白σ1s是建立病毒血症和血源性病毒传播所必需的。但是，呼肠孤病毒复制周期中σ1s的功能尚不清楚。在这项研究中，我们发现在猿猴病毒40（SV40）永生化内皮细胞（SVEC），小鼠胚胎成纤维细胞，人脐静脉内皮细胞（HUVEC）和T84人结肠上皮细胞中有效呼肠孤病毒复制中需要σ1s。在这些细胞系中的每一种中，野生型呼肠孤病毒产生的病毒效价均比σ1s缺陷型突变体高。呼肠孤病毒感染的早期事件不需要σ1s蛋白，这一事实证明了野生型和σ1s-null病毒之间的感染力没有差异。然而，野生型病毒产生的病毒蛋白水平明显高于σ1s缺陷株。病毒复制的差异不是由病毒转录或蛋白质稳定性的差异引起的。我们进一步发现σ1s蛋白对于细胞杀伤和诱导I型干扰素反应是必不可少的。在没有σ1的情况下，病毒工厂（VF）的成熟受到损害，但足以支持低水平的呼肠孤病毒复制。在一起，我们的结果表明σ1s并非绝对必需的病毒蛋白生产，而是加强呼肠孤病毒蛋白的表达以促进呼肠孤病毒的复制。我们的发现表明，σ1s通过促进有效的病毒蛋白合成，从而在呼肠病毒传播到血液的细胞中促进有效的病毒蛋白合成，从而实现了血源性呼肠孤病毒的传播。

重要性血源性传播是许多病毒发病机理中的关键步骤。对于呼肠孤病毒，通过血液传播病毒需要非结构蛋白σ1s。但是，σ1s促进呼肠孤病毒传播的机制尚不清楚。在这项研究中，我们确定了σ1s是呼肠孤病毒蛋白表达的病毒介体。我们发现了几种培养的细胞系，其中σ1s是有效的呼肠孤病毒复制所必需的。在这些细胞中，野生型病毒比σ1s缺陷型突变体产生更高水平的病毒蛋白。σ1s蛋白不是病毒mRNA转录或病毒蛋白稳定性所必需的。由于在没有σ1s的情况下合成了降低水平的病毒蛋白，因此病毒工厂的成熟受到损害，并且产生的病毒后代明显减少。在一起