Osteopontin plays a pivotal role in increasing severity of respiratory syncytial virus infection.
Osteopontin plays a pivotal role in increasing severity of respiratory syncytial virus infection.
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DOI：
10.1371/journal.pone.0192709
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Mohapatra SS
中科院分区：
文献类型：
--
作者：
Sampayo-Escobar V;Green R;Cheung MB;Bedi R;Mohapatra S;Mohapatra SS
严重呼吸道合胞病毒（RSV）感染易感性的分子机制尚不清楚。在此，我们报道了骨桥蛋白（OPN）在人上皮细胞中调控RSV感染的作用，以及白细胞介素-1β (IL-1β)是RSV感染后不久分泌的一种细胞因子，当持续表达可诱导OPN表达导致病毒感染增加。我们首先比较了两种人上皮细胞系HEK-293和HEp-2中OPN的表达。与HEp-2相比，HEK-293在RSV感染时表达低水平的前caspase-1，导致IL-1β表达降低。我们发现，与HEp-2相比，在rsv感染的HEK-293细胞中，低IL-1β水平与诱导OPN表达的延迟存在相关性。这一现象可以部分解释HEp-2细胞对RSV感染的高易感性而HEK-293细胞的中等易感性。此外，表达低水平前caspase-1的HEK-293细胞在RSV感染时表现出IL-1β表达降低和OPN表达延迟。与人il -1β孵育的HEK-293细胞在RSV感染后显示出OPN表达的剂量依赖性增加。此外，用rOPN孵育可增加RSV病毒载量。此外，与感染实验室RSV菌株rA2的小鼠相比，感染粘液源性RSV菌株RSV- l19f的HEp-2细胞或小鼠的OPN水平升高。与rA2相比，这与RSV-L19F感染后OPN水平升高有关。总之，这些结果表明，OPN表达的增加部分受IL-1β的调节，IL-1β与OPN信号的相互作用可能在RSV感染的传播中起关键作用。
The molecular mechanisms underlying susceptibility to severe respiratory syncytial virus (RSV) infection remain poorly understood. Herein, we report on the role of osteopontin (OPN) in regulation of RSV infection in human epithelial cells and how interleukin-1 beta (IL-1β), a cytokine secreted soon after RSV infection, when persistently expressed can induce OPN expression leading to increased viral infection. We first compared OPN expression in two human epithelial cell lines: HEK-293 and HEp-2. In contrast to HEp-2, HEK-293 expresses low levels of pro-caspase-1 resulting in decreased IL-1β expression in response to RSV infection. We found a correlation between low IL-1β levels and a delay in induction of OPN expression in RSV-infected HEK-293 cells compared to HEp-2. This phenomenon could partially explain the high susceptibility of HEp-2 cells to RSV infection versus the moderate susceptibility of HEK-293 cells. Also, HEK-293 cells expressing low levels of pro-caspase-1 exhibit decreased IL-1β expression and delayed OPN expression in response to RSV infection. HEK-293 cells incubated with human rIL-1β showed a dose-dependent increase in OPN expression upon RSV infection. Also, incubation with rOPN increased RSV viral load. Moreover, HEp-2 cells or mice infected with a mucogenic RSV strain RSV-L19F showed elevated levels of OPN in contrast to mice infected with the laboratory RSV strain rA2. This correlated with elevated levels of OPN following infection with RSV-L19F compared to rA2. Together, these results demonstrate that increased OPN expression is regulated in part by IL-1β, and the interplay between IL-1β and OPN signaling may play a pivotal role in the spread of RSV infection.
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