Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai)/ School of Marine Sciences, Sun Yat-sen University, Guangzhou, P. R. People's Republic of China.
State Key Laboratory of Biocontrol/ School of Life Sciences, Sun Yat-sen University, Guangzhou, P. R. People's Republic of China.
Emerg Microbes Infect. 2020 Dec;9(1):390-412. doi: 10.1080/22221751.2020.1729068.
Emerging studies have indicated that some penaeidins restrict virus infection; however, the mechanism(s) involved are poorly understood. In the present study, we uncovered that penaeidins are a novel family of antiviral effectors against white spot syndrome virus (WSSV), which antagonize the envelope proteins to block viral entry. We found that the expression levels of four identified penaeidins from , including , , , and , were significantly induced in hemocytes during the early stage of WSSV infection. Knockdown of each penaeidin via RNA interference resulted in elevated viral loads and rendered shrimp more susceptible to WSSV, while the survival rate was rescued via the injection of recombinant penaeidins. All penaeidins, except PEN4, were shown to interact with several envelope proteins of WSSV, and all four penaeidins were observed to be located on the outer surface of the WSSV virion. Co-incubation of each recombinant penaeidin with WSSV inhibited virion internalization into hemocytes. More importantly, we found that PEN2 competitively bound to the envelope protein VP24 to release it from polymeric immunoglobulin receptor (pIgR), the cellular receptor required for WSSV infection. Moreover, we also demonstrated that BigPEN was able to bind to VP28 of WSSV, which disrupted the interaction between VP28 and Rab7 - the Rab GTPase that contributes to viral entry by binding with VP28. Taken together, our results demonstrated that penaeidins interact with the envelope proteins of WSSV to block multiple viral infection processes, thereby protecting the host against WSSV.
新兴研究表明，一些肽聚糖可以限制病毒感染；然而，其涉及的机制仍知之甚少。在本研究中，我们揭示了肽聚糖是一类针对白斑综合征病毒（WSSV）的新型抗病毒效应因子，可拮抗包膜蛋白以阻止病毒进入。我们发现，在 WSSV 感染的早期阶段，来自 的 4 种鉴定的肽聚糖（包括 PEN1、PEN2、PEN3 和 PEN4）在血细胞中的表达水平显著上调。通过 RNA 干扰敲低每种肽聚糖都会导致病毒载量升高，使虾更容易感染 WSSV，而通过注射重组肽聚糖则可以挽救存活率。除 PEN4 外，所有肽聚糖都与 WSSV 的几种包膜蛋白相互作用，并且所有 4 种肽聚糖都观察到位于 WSSV 病毒粒子的外表面。每种重组肽聚糖与 WSSV 的共孵育抑制了病毒粒子进入血细胞的内化。更重要的是，我们发现 PEN2 竞争性结合包膜蛋白 VP24，将其从多聚免疫球蛋白受体（pIgR）上释放出来，pIgR 是 WSSV 感染所需的细胞受体。此外，我们还证明 BigPEN 能够与 WSSV 的 VP28 结合，从而破坏 VP28 与 Rab7 之间的相互作用，Rab7 是一种 Rab GTPase，通过与 VP28 结合有助于病毒进入。总之，我们的结果表明肽聚糖与 WSSV 的包膜蛋白相互作用，阻断多种病毒感染过程，从而保护宿主免受 WSSV 的侵害。
