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The roles of grouper clathrin light chains in regulating the infection of a novel marine DNA virus Singapore grouper iridovirus

机译:石斑鱼网格蛋白轻链在调节新型海洋DNA病毒新加坡石斑鱼虹膜病毒感染中的作用

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摘要

Clathrins, composed of clathrin heavy chains (CHCs) and clathrin light chains (CLCs), are usually hijacked by viruses for infection. However, the role of CLCs, especially in regulating fish virus infection, remains poorly understood. Here, two isoforms of CLCs were cloned from the red-spotted grouper (Epinephelus akaara) (EaCLCa and EaCLCb). Both EaCLC transcripts were expressed in all examined tissues, and the expression of EaCLCa was much higher than that of EaCLCb. Over-expressing EaCLCa-W119R mutant significantly reduced Singapore grouper iridovirus (SGIV) infectivity. However, no effect of EaCLCb-W122R on SGIV infection was observed. The detailed steps were further studied, mainly including virus attachment, entry and the following transport to early endosomes. EaCLCa-W119R mutant notably inhibited internalization of SGIV particles with no effect on SGIV attachment. Furthermore, EaCLCa-W119R mutant obviously impaired the delivery of SGIV to early endosomes after virus internalization. In addition, the EaCLCa-W119R mutant markedly reduced the colocalization of SGIV and actin. However, EaCLCb is not required for such events during SGIV infection. Taken together, these results demonstrate for the first time that EaCLCa and EaCLCb exerted different impacts on iridovirus infection, providing a better understanding of the mechanisms of SGIV infection and opportunities for the design of new antiviral strategies.
机译:网格蛋白由网格蛋白重链(CHC)和网格蛋白轻链(CLC)组成,通常会被病毒劫持以进行感染。但是,对CLC的作用,特别是在调节鱼病毒感染中的作用,仍然知之甚少。在这里,从红斑石斑鱼(Epinephelus akaara)(EaCLCa和EaCLCb)克隆了两种CLC亚型。在所有检查的组织中均表达了两种EaCLC转录本,并且EaCLCa的表达远高于EaCLCb的表达。过表达的EaCLCa-W119R突变体显着降低了新加坡石斑鱼虹膜病毒(SGIV)的感染性。但是,未观察到EaCLCb-W122R对SGIV感染的影响。进一步研究了详细步骤,主要包括病毒附着,进入和随后转运至早期内体。 EaCLCa-W119R突变体显着抑制SGIV颗粒的内在化,而对SGIV的附着没有影响。此外,EaCLCa-W119R突变体明显削弱了病毒内化后SGIV向早期内体的传递。此外,EaCLCa-W119R突变体显着降低了SGIV和肌动蛋白的共定位。但是,SGIV感染期间此类事件不需要EaCLCb。综上所述,这些结果首次证明EaCLCa和EaCLCb对虹膜病毒感染有不同的影响,从而使人们对SGIV感染的机制有了更好的了解,并为设计新的抗病毒策略提供了机会。

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