自噬在猪繁殖与呼吸综合征病毒感染中的作用机制研究进展

doi:10.3864/j.issn.0578-1752.2025.04.013

摘要/Abstract

摘要：

猪繁殖与呼吸综合征病毒（porcine reproductive and respiratory syndrome virus，PRRSV）是一种具有囊膜的单股正链RNA动脉炎病毒。PRRSV感染猪后引起猪繁殖与呼吸综合征（porcine reproductive and respiratory syndrome，PRRS），导致妊娠母猪流产、死胎、弱胎和木乃伊胎以及各年龄段猪呼吸系统疾病，对全球养猪业造成巨大的经济损失。全面解析PRRSV感染机制有助于防控PRRS，助力生猪产业高质量发展。自噬是一种依赖于溶酶体对异常蛋白质、受损细胞器、入侵病原微生物等进行降解回收的过程，包括巨自噬、微自噬和分子伴侣介导的自噬（chaperone-mediated autophagy，CMA）3种类型。其中，巨自噬是目前研究最多的自噬类型，可进一步分为非选择性自噬和选择性自噬。自噬在维持细胞稳态、控制细胞器质量、运输胞内物质等生理过程中发挥着重要作用，还影响神经退行性疾病、自身免疫病、癌症等多种疾病的发生和发展。此外，自噬作为一种防御机制，能够清除入侵宿主细胞的病毒；然而，病毒进化出一系列策略拮抗自噬降解甚至利用自噬为自身感染服务。文章通过笔者自身的研究经历和近年来自噬在PRRSV感染过程中的研究报道，系统梳理介绍了自噬在PRRSV感染中发挥的双重作用：一方面，PRRSV非结构蛋白和结构蛋白通过多种途径诱导包括内质网自噬、线粒体自噬、聚集体自噬、脂噬等选择性自噬在内的巨自噬和CMA，随后这些诱导的巨自噬和CMA参与PRRSV复制、拮抗细胞凋亡、抑制宿主免疫反应等过程促进病毒感染；另一方面，宿主细胞通过内质网自噬等选择性巨自噬和CMA降解PRRSV非结构蛋白、激活抗病毒免疫应答等抑制病毒感染，以期从自噬角度深入揭示PRRSV感染机制。另外，文章还通过总结自噬在PRRSV感染中的作用机制，提出该研究领域仍然存在争议或尚未解答的科学问题，为今后研究提供线索；同时通过列举靶向自噬的抗病毒研究，提出自噬可作为抗PRRSV策略研发的潜在靶点，为防控PRRS提供新的思路。

关键词: 猪繁殖与呼吸综合征病毒, 感染, 自噬, 作用机制, 抗病毒靶点

Abstract:

Porcine reproductive and respiratory syndrome virus (PRRSV) is an enveloped single-stranded positive sense RNA arterivirus. Infection by PRRSV results in porcine reproductive and respiratory syndrome (PRRS), characterized by abortions, stillbirths, weak-born piglets, and mummified fetuses in sows as well as respiratory diseases in pigs of all ages. PRRSV has caused tremendous economic losses to the global swine industry. Comprehensive investigation on PRRSV infection would be beneficial for the prevention and control of PRRS, and contribute to the high-quality development of the swine industry. Autophagy is a lysosome-dependent degradation and recycling process for abnormal proteins, damaged organelles, and invading pathogens. It comprises macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA),among which macroautophagy has been most extensively investigated so far, and is classified as non-selective autophagy and selective autophagy. Autophagy plays crucial roles in maintaining cellular homeostasis, controlling the quality of organelles, and transporting intracellular materials. Furthermore, autophagy is involved in diverse diseases, such as neurodegenerative diseases, autoimmune diseases, and cancers. Moreover, autophagy is a potent defense response to eliminate invading viruses, while viruses have evolved multiple strategies to subvert the autophagic degradation or even exploit autophagy for their own benefits. This review systematically scrutinized recent research progress on the roles and mechanisms of autophagy involved in PRRSV infection, and elaborated that autophagy played a dual role during PRRSV infection. On the one hand, PRRSV non-structural and structural proteins triggered macroautophagy (including reticulophagy, mitophagy, aggrephagy, and lipophagy) and CMA via a variety of mechanisms; in turn, macroautophagy and CMA facilitated PRRSV infection by participation in viral replication, antagonism of apoptosis, and inhibition of host immunity. On the other hand, selective autophagy (eg., reticulophagy) and CMA suppressed PRRSV infection by degradation of viral non-structural proteins and activation of antiviral immune responses. This review actually deepend the understanding of PRRSV infection from the autophagy perspective. In addition, this review summarized and raised certain controversial or unsolved issues, which provided clues for future studies on the roles and mechanisms of autophagy involved in PRRSV infection; in the meantime, this review illustrated and supported potential targets against autophagy for developing antiviral interventions to restrain PRRS epidemics.

Key words: PRRSV, infection, autophagy, roles and mechanisms, antiviral targets

李睿, 梁跃, 白杨, 张桂悦, 王楠楠, 乔松林, 张改平. 自噬在猪繁殖与呼吸综合征病毒感染中的作用机制研究进展[J]. 中国农业科学, 2025, 58(4): 792-801.

LI Rui, LIANG Yue, BAI Yang, ZHANG GuiYue, WANG NanNan, QIAO SongLin, ZHANG GaiPing. Research Progress on the Roles and Mechanisms of Autophagy Involved in Porcine Reproductive and Respiratory Syndrome Virus Infection[J]. Scientia Agricultura Sinica, 2025, 58(4): 792-801.

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