Bta-miR-98 Suppresses Replication of Caprine Parainfluenza Virus Type 3 Through Inhibiting Apoptosis by Targeting Caspase-3
Bta-miR-98 Suppresses Replication of Caprine Parainfluenza Virus Type 3 Through Inhibiting Apoptosis by Targeting Caspase-3
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DOI：
10.3389/fimmu.2020.01575
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发表时间：
2020-08
影响因子：
7.3
通讯作者：
Jizong Li;Chunyan Zhong;Zheng Liao;Li-Guo Mao;Wenliang Li;Min-xuan Sun;Maojun Liu;Xinqin Ji
中科院分区：
文献类型：
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作者：
Jizong Li;Chunyan Zhong;Zheng Liao;Li-Guo Mao;Wenliang Li;Min-xuan Sun;Maojun Liu;Xinqin Ji
山羊副流感病毒 3 型 (CPIV3) 是一种新出现的呼吸道病原体，影响中国乃至世界其他国家的绵羊和山羊产业。越来越多的证据表明，microRNA 在调节病毒与宿主的相互作用中发挥着重要作用，并且可以抑制或促进病毒复制。在这项研究中，我们通过形态学变化和流式细胞术确定，CPIV3 感染诱导 Madin-Darby 牛肾 (MDBK) 细胞凋亡。 Caspase 活性和促凋亡基因的表达进一步表明 CPIV3 通过激活内在和外在途径诱导细胞凋亡。我们还证明了 bta-microRNA-98 (bta-miR-98) 参与调节 CPIV3 诱导的细胞凋亡。 Bta-miR-98 在感染 CPIV3 的 MDBK 细胞中下调。 bta-miR-98 的过表达显着降低了 caspase-3、-8 和 -9 的活性。相反，抑制 bta-miR-98 则产生完全相反的效果。此外，我们的数据表明 bta-miR-98 通过调节细胞凋亡显着影响 CPIV3 复制。重要的是，我们发现 bta-miR-98 通过靶向凋亡效应子 caspase-3 来调节 CPIV3 诱导的凋亡。总的来说，我们的结果可能表明 CPIV3 感染诱导细胞凋亡并下调 bta-miR-98 的水平，并且该 miRNA 通过影响细胞凋亡来调节病毒复制。这项研究有助于我们了解 CPIV3 发病机制的分子机制。
Caprine parainfluenza virus type 3 (CPIV3) is an emerging respiratory pathogen that affects the sheep and goat industry in China and possibly other countries around the world. Accumulating evidence suggests that microRNAs play important roles in regulating virus-host interactions and can suppress or facilitate viral replication. In this study, we showed that CPIV3 infection induced apoptosis in Madin-Darby bovine kidney (MDBK) cells, as determined by morphological changes and flow cytometry. Caspase activity and the expression of pro-apoptotic genes further indicated that CPIV3 induced apoptosis by activating both the intrinsic and extrinsic pathways. We also demonstrated the involvement of bta-microRNA-98 (bta-miR-98) in regulating CPIV3-induced apoptosis. Bta-miR-98 was downregulated in MDBK cells infected with CPIV3. Overexpression of bta-miR-98 significantly decreased the activities of caspase-3, −8, and −9. Conversely, inhibition of bta-miR-98 had completely opposite effects. Furthermore, our data showed that bta-miR-98 markedly affected CPIV3 replication by regulating apoptosis. Importantly, we found that bta-miR-98 modulated CPIV3-induced apoptosis by targeting caspase-3, an effector of apoptosis. Collectively, our results may suggest that CPIV3 infection induced apoptosis and downregulated the levels of bta-miR-98, and this miRNA regulated viral replication through effected apoptosis. This study contributes to our understanding of the molecular mechanisms underlying CPIV3 pathogenesis.