Porcine sapovirus replication is restricted by the type I interferon response in cell culture.
Porcine sapovirus replication is restricted by the type I interferon response in cell culture.
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DOI：
10.1099/vir.0.071365-0
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发表时间：
2015-01
期刊：
影响因子：
--
通讯作者：
Cho KO
中科院分区：
文献类型：
--
作者：
Hosmillo M;Sorgeloos F;Hiraide R;Lu J;Goodfellow I;Cho KO
猪痘病毒属（Porcine sapovirus，PSaV）是杯状病毒科（Caliciviridae）中唯一一种具有细胞培养和反向遗传学系统的痘病毒属（Sapovirus）。当与仔猪模型相结合时，这些方法提供了一个系统，以了解沙波病毒致病的分子基础。然而，PSaV在细胞培养物中的复制受到限制，显示出对胆汁酸的绝对需求，并且产生比其他杯状病毒更低水平的感染性病毒。胆汁酸的作用以前被认为与信号转导和转录激活因子（STAT 1）介导的信号通路的减少有关。在目前的研究中，我们观察到，即使在胆汁酸的存在下，细胞培养物中的PSaV复制也受到感染细胞产生的可溶性因子的限制。这种效应至少部分是由于分泌的IFN，因为用重组猪IFN-β处理细胞导致病毒复制显著减少。此外，在PSaV感染期间，IFN介导的信号传导途径（IFN、STAT 1和2′，5 ′-寡腺苷酸合成酶）被激活。在缺乏诱导或应答IFN的能力的细胞系中，PSaV生长的表征显示感染性病毒产生增加100-150倍，表明胆汁酸的主要作用不是先天免疫应答的失活。此外，使用IFN缺陷型细胞系能够更有效地从cDNA构建体中回收PSaV。总体而言，高效的细胞培养和反向遗传学系统建立在这里的PSaV突出了先天免疫反应的关键作用，在限制PSaV感染，并应大大促进进一步的分子研究sapovirus宿主细胞相互作用。
Porcine sapovirus (PSaV) of the family Caliciviridae, is the only member of the genus Sapovirus with cell culture and reverse genetics systems. When combined with the piglet model, these approaches provide a system to understand the molecular basis of sapovirus pathogenesis. The replication of PSaV in cell culture is, however, restricted, displaying an absolute requirement for bile acids and producing lower levels of infectious virus than other caliciviruses. The effect of bile acids has previously been linked to a reduction in the signal transducer and activator of transcription (STAT1)-mediated signalling pathway. In the current study, we observed that even in the presence of bile acids, PSaV replication in cell culture was restricted by soluble factors produced from infected cells. This effect was at least partially due to secreted IFN because treatment of cells with recombinant porcine IFN-β resulted in significantly reduced viral replication. Moreover, IFN-mediated signalling pathways (IFN, STAT1 and the 2′,5′-oligoadenylate synthetase) were activated during PSaV infection. Characterization of PSaV growth in cell lines deficient in their ability to induce or respond to IFN showed a 100–150-fold increase in infectious virus production, indicating that the primary role of bile acids was not the inactivation of the innate immune response. Furthermore, the use of IFN-deficient cell lines enabled more efficient recovery of PSaV from cDNA constructs. Overall, the highly efficient cell culture and reverse genetics system established here for PSaV highlighted the key role of the innate immune response in the restriction of PSaV infection and should greatly facilitate further molecular studies on sapovirus host–cell interactions.
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