Porcine Reproductive and Respiratory Syndrome Virus Utilizes Viral Apoptotic Mimicry as an Alternative Pathway To Infect Host Cells
Porcine Reproductive and Respiratory Syndrome Virus Utilizes Viral Apoptotic Mimicry as an Alternative Pathway To Infect Host Cells
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DOI：
10.1128/jvi.00709-20
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发表时间：
2020-06
影响因子：
5.4
通讯作者：
Xin Wei;Rui Li;S. Qiao;Xin-xin Chen;G. Xing;Gaiping Zhang
中科院分区：
文献类型：
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作者：
Xin Wei;Rui Li;S. Qiao;Xin-xin Chen;G. Xing;Gaiping Zhang
PRRS给全球养猪业造成了巨大的经济损失。其病原体PRRSV通过低pH依赖的网格蛋白介导的内吞作用感染宿主细胞，并且在该过程中CD 163是不可缺少的。PRRSV是否存在其他感染途径引起了人们的兴趣。在这里，我们发现，PRRSV暴露其包膜上的PS和伪装成凋亡碎片。PS受体TIM-1/4识别PRRSV，并通过CD 163依赖的巨胞饮作用诱导下游信号通路介导病毒感染。目前的工作加深了我们对PRRSV感染的理解，并为开发针对该病毒的药物和疫苗提供了线索。摘要由猪繁殖与呼吸综合征病毒（PRRS）引起的猪繁殖与呼吸综合征（PRRS）给全球养猪业造成了巨大的经济损失。先前已证明PRRSV感染是通过低pH依赖性网格蛋白介导的内吞作用，并且CD 163在病毒感染期间充当必需受体。尽管有很多研究集中在它，PRRSV感染仍有待充分阐明。在这项研究中，我们证明，PRRSV外化的磷脂酰丝氨酸（PS）的包膜病毒的凋亡模拟和感染宿主细胞通过T细胞免疫球蛋白和粘蛋白结构域（TIM）诱导和CD 163参与的巨胞饮作为一种替代途径。详细地，我们确定PS受体TIM-1/4识别并与PRRSV相互作用，作为病毒凋亡模拟，随后通过下游Rho GTP酶Rac 1、细胞分裂控制蛋白42（Cdc 42）和p21激活的激酶1（Pak 1）诱导巨胞饮。总之，这些结果扩大了我们对PRRSV感染的认识，这将支持对PRRS预防和控制的影响。PRRS给全球养猪业造成了巨大的经济损失。其病原体PRRSV通过低pH依赖的网格蛋白介导的内吞作用感染宿主细胞，并且在该过程中CD 163是不可缺少的。PRRSV是否存在其他感染途径引起了人们的兴趣。在这里，我们发现，PRRSV暴露其包膜上的PS和伪装成凋亡碎片。PS受体TIM-1/4识别PRRSV，并通过CD 163依赖的巨胞饮作用诱导下游信号通路介导病毒感染。目前的工作加深了我们对PRRSV感染的理解，并为开发针对该病毒的药物和疫苗提供了线索。
PRRS has caused huge economic losses to pig farming worldwide. Its causative agent, PRRSV, infects host cells through low pH-dependent clathrin-mediated endocytosis and CD163 is indispensable during the process. Whether there exist alternative infection pathways for PRRSV arouses our interest. Here, we found that PRRSV exposed PS on its envelope and disguised as apoptotic debris. The PS receptor TIM-1/4 recognized PRRSV and induced the downstream signaling pathway to mediate viral infection via CD163-dependent macropinocytosis. The current work deepens our understanding of PRRSV infection and provides clues for the development of drugs and vaccines against the virus. ABSTRACT Porcine reproductive and respiratory syndrome (PRRS), caused by PRRS virus (PRRSV), has led to enormous economic losses in global swine industry. Infection by PRRSV is previously shown to be via low pH-dependent clathrin-mediated endocytosis, and CD163 functions as an essential receptor during viral infection. Despite much research focusing on it, PRRSV infection remains to be fully elucidated. In this study, we demonstrated that PRRSV externalized phosphatidylserine (PS) on the envelope as viral apoptotic mimicry and infected host cells through T-cell immunoglobulin and mucin domain (TIM)-induced and CD163-involved macropinocytosis as an alternative pathway. In detail, we identified that PS receptor TIM-1/4 recognized and interacted with PRRSV as viral apoptotic mimicry and subsequently induced macropinocytosis by the downstream Rho GTPases Rac1, cell division control protein 42 (Cdc42), and p21-activated kinase 1 (Pak1). Altogether, these results expand our knowledge of PRRSV infection, which will support implications for the prevention and control of PRRS. IMPORTANCE PRRS has caused huge economic losses to pig farming worldwide. Its causative agent, PRRSV, infects host cells through low pH-dependent clathrin-mediated endocytosis and CD163 is indispensable during the process. Whether there exist alternative infection pathways for PRRSV arouses our interest. Here, we found that PRRSV exposed PS on its envelope and disguised as apoptotic debris. The PS receptor TIM-1/4 recognized PRRSV and induced the downstream signaling pathway to mediate viral infection via CD163-dependent macropinocytosis. The current work deepens our understanding of PRRSV infection and provides clues for the development of drugs and vaccines against the virus.