猪繁殖与呼吸综合征病毒结构蛋白 GP3 调节紧密连接蛋白 4 促进感染的早期阶段。
Porcine Reproductive and Respiratory Syndrome Virus Structural Protein GP3 Regulates Claudin 4 To Facilitate the Early Stages of Infection.
机构信息
Department of Fundamental Veterinary Medicine, College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an, Shandong, China.
Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Tai'an, Shandong, China.
出版信息
J Virol. 2020 Sep 29;94(20). doi: 10.1128/JVI.00124-20.
Claudins (CLDN) are a family of proteins that represent the most important components of tight junctions, where they establish the paracellular barrier that controls the flow of molecules in the intercellular space between epithelial cells. Several types of viruses make full use of CLDN to facilitate entry into cells. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important pathogens in the swine industry. In this study, we found that CLDN4 functions as an anti-PRRSV factor by blocking its absorption during the early stages of infection. The small extracellular loop (ECL2) of CLDN4 restricted the viral particles outside cells by binding to GP3. A novel function of GP3-mediated regulation of transcription was suggested. CLDN4 can be decreased through downregulating the level of transcription by ubiquitinating the transcription factor, SP1. The mechanism by which highly pathogenic PRRSV infects the epithelium was proposed. Importantly, ECL2 was found to block PRRSV absorption and infection and neutralize the virus. A more in-depth understanding of PRRSV infection is described, and novel therapeutic antiviral strategies are discussed. In the present study, the role of CLDN4 in PRRSV infection was studied. The results showed that CLDN4 blocked absorption into cells and restricted extracellular viral particles via the interaction between the CLDN4 small extracellular loop, ECL2, and the viral surface protein GP3. GP3 was found to downregulate CLDN4 through ubiquitination of the transcription factor SP1 to facilitate viral entry. The mechanism by which highly pathogenic PRRSV infects the epithelium is suggested. A novel function of GP3 in regulating gene transcription was discovered. Moreover, ECL2 could block PRRSV absorption and infection, as well as neutralizing the virus in the supernatant, which may lead to the development of novel therapeutic antiviral strategies.
紧密连接相关蛋白（Claudin，CLDN）是紧密连接的重要组成部分，它们构成了细胞旁的屏障，控制着上皮细胞之间细胞间隙中分子的流动。几种类型的病毒充分利用 CLDN 来促进进入细胞。猪繁殖与呼吸综合征病毒（Porcine reproductive and respiratory syndrome virus，PRRSV）是养猪业最重要的病原体之一。在这项研究中，我们发现 CLDN4 通过在感染早期阻止病毒的吸收来发挥抗 PRRSV 作用。CLDN4 的小细胞外环（Small extracellular loop，ECL2）通过与 GP3 结合，将病毒粒子限制在细胞外。提出了 GP3 介导的转录调控的新功能。CLDN4 可以通过泛素化转录因子 SP1 来降低转录水平，从而降低。提出了高致病性 PRRSV 感染上皮细胞的机制。重要的是，发现 ECL2 可通过阻断 PRRSV 的吸收和感染并中和病毒来阻断 PRRSV 的吸收和感染。更深入地了解 PRRSV 感染，并讨论了新的治疗性抗病毒策略。在本研究中，研究了 CLDN4 在 PRRSV 感染中的作用。结果表明，CLDN4 通过 CLDN4 的小细胞外环 ECL2 与病毒表面蛋白 GP3 之间的相互作用，阻断病毒进入细胞并限制细胞外的病毒粒子。发现 GP3 通过泛素化转录因子 SP1 下调 CLDN4，从而促进病毒进入。提出了高致病性 PRRSV 感染上皮细胞的机制。发现了 GP3 在调节基因转录中的新功能。此外，ECL2 可阻断 PRRSV 的吸收和感染，并中和上清液中的病毒，这可能导致新的治疗性抗病毒策略的发展。
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