Elastase-mediated membrane fusion of highly pathogenic porcine reproductive and respiratory syndrome virus at host cell surface
Elastase-mediated membrane fusion of highly pathogenic porcine reproductive and respiratory syndrome virus at host cell surface
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DOI：
10.1016/j.vetmic.2020.108851
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发表时间：
2020-11-01
影响因子：
3.3
通讯作者：
Zhang, Gaiping
中科院分区：
文献类型：
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作者：
Hou, Jie;Li, Rui;Zhang, Gaiping
包膜病毒的感染包括胞吞作用和/或质膜上的膜融合，其中宿主细胞蛋白酶发挥重要作用。其中，弹性蛋白酶介导的感染已被记录的几个包膜病毒。猪繁殖与呼吸综合征病毒（Porcine reproductive and respiratory syndrome virus，PRRSV）是影响全球养猪业的一个重要因素，它通过低pH值依赖的网格蛋白介导的内吞作用（clathrin mediated endocytosis，CME）感染宿主细胞，并在循环核内体中进行膜融合。在目前的研究中，我们确定，弹性蛋白酶显着升高，在肺组织中的高致病性PRRSV（HP-PRRSV）感染的猪相比，模拟感染的。我们随后证明，弹性蛋白酶有助于HP-PRRSV感染MARC-145细胞和猪肺泡巨噬细胞（PAM）。机制上，HP-PRRSV通过弹性蛋白酶介导的膜融合在细胞表面进入宿主细胞，不依赖于低pH和CME，并且其糖蛋白5（GP 5）在此过程中被蛋白酶切割。这些研究结果加深了对HP-PRRSV感染的认识，对该病的预防和控制具有重要意义。
Infection by enveloped viruses includes endocytosis and/or membrane fusion at the plasma membrane, where host cell proteases play an essential role. Among them, elastase-mediated infection has been documented for several enveloped viruses. Porcine reproductive and respiratory syndrome virus (PRRSV), an economically critical factor in global swine industry, is previously reported to infect host cells via low pH-dependent clathrin-mediated endocytosis (CME) and undergo membrane fusion in recycling endosomes. In the current study, we identified that elastase was significantly elevated in the lung tissues of highly pathogenic PRRSV (HP-PRRSV)-infected pigs compared to the mock-infected ones. We subsequently demonstrated that elastase contributed to HP-PRRSV infection in both MARC-145 cells and porcine alveolar macrophages (PAMs). Mechanistically, HP-PRRSV entered host cells at the cell surface via elastase-mediated membrane fusion, independent of low pH and CME, and its glycoprotein 5 (GP5) was cleaved by the protease during this process. All these findings deepen our understanding of HP-PRRSV infection, and are beneficial for prevention and control of the disease.