Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic losses to the pork industry. The present study showed that Yansuanmalingua (YASML) can inhibit type 2 PRRSV replication using plaque assay, quantitative reverse transcriptase‐polymerase chain reaction, and immunofluorescence assay. Furthermore, inhibition of PRRSV replication was shown to be related to Toll‐like receptor 3 (TLR3)‐dependent apoptosis‐induction by YASML in the PRRSV‐infected MARC‐145, and TLR3‐dependent apoptosis‐induction by YASML was found to suppress PRRSV replication via the activation of caspase‐8 and caspase‐3 pathways, respectively. Meanwhile, activation of the caspase‐3 pathway seemed to be related to the downregulation of myeloid cell leukemia 1 (Mcl‐1) expression. Our results showed that YASML‐induced TLR3‐dependent apoptosis could be blocked by a pan‐caspase inhibitor and small interfering RNA against TLR3. In conclusion, the present study demonstrates that YASML exerts its anti‐PRRSV effect by activating the caspase‐8/caspase‐3 signaling pathway and by negatively regulating Mcl‐1 expression. These findings not only provide new insights into the molecular mechanism of YASML inhibition of PRRSV replication via the TLR3‐dependent apoptosis pathway but also suggest potential, new antiviral drugs by expressing caspase‐3 or down expressing Mcl‐1.

中文翻译：

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燕酸马林瓜通过激活caspase-8凋亡通路抑制2型猪繁殖与呼吸综合征病毒复制

猪繁殖与呼吸综合征病毒 (PRRSV) 给养猪业造成重大经济损失。本研究表明，Yasuanmalingua (YASML) 可以通过噬斑测定、定量逆转录酶-聚合酶链反应和免疫荧光测定抑制 2 型 PRRSV 复制。此外，在 PRRSV 感染的 MARC-145 中，PRRSV 复制的抑制被证明与 YASML 对 Toll 样受体 3 (TLR3) 依赖性细胞凋亡诱导有关，并且发现 YASML 对 TLR3 依赖性细胞凋亡诱导可抑制 PRRSV分别通过激活 caspase-8 和 caspase-3 途径进行复制。同时，caspase-3通路的激活似乎与髓细胞白血病1（Mcl-1）表达的下调有关。我们的结果表明，泛半胱天冬酶抑制剂和针对 TLR3 的小干扰 RNA 可以阻断 YASML 诱导的 TLR3 依赖性细胞凋亡。总之，本研究表明 YASML 通过激活 caspase-8/caspase-3 信号通路和负调节 Mcl-1 表达来发挥其抗 PRRSV 作用。这些发现不仅为 YASML 通过 TLR3 依赖性细胞凋亡途径抑制 PRRSV 复制的分子机制提供了新的见解，而且还通过表达 caspase-3 或向下表达 Mcl-1 提出了潜在的新型抗病毒药物。