The Capsid Proteins of Aleutian Mink Disease Virus Activate Caspases and Are Specifically Cleaved during Infection
The Capsid Proteins of Aleutian Mink Disease Virus Activate Caspases and Are Specifically Cleaved during Infection
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DOI：
10.1128/jvi.01917-09
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发表时间：
2010-03-01
影响因子：
5.4
通讯作者：
Qiu, Jianming
中科院分区：
文献类型：
--
作者：
Cheng, Fang;Chen, Aaron Yun;Qiu, Jianming
阿留申水貂病病毒 (AMDV) 是细小病毒科阿留申水貂病毒属中唯一已知的成员。它是水貂阿留申病的病原体。我们之前已经证明，在 AMDV 感染期间和衣壳表达构建体转染后，存在分子量约为 26 kDa 的小蛋白（J. Qiu, F. Cheng, L. R. Burger, and D. Pintel, J. Virol. 80:654-662, 2006）。在这项研究中，我们报告说，在病毒感染过程中，衣壳蛋白在天冬氨酸残基 420 (D420) 处被特异性切割，从而产生了先前观察到的切割产物。 D420 处单个氨基酸残基的突变消除了特异性切割。衣壳蛋白在克兰德尔猫肾 (CrFK) 细胞中单独表达，再现了病毒感染时衣壳蛋白的裂解。更重要的是，衣壳蛋白单独表达可诱导活性 caspase，其中 caspase-10 活性最高。活性半胱天冬酶反过来在体内裂解衣壳蛋白。我们的结果还表明，活性 caspase-7 在体外特异性切割 D420 处的衣壳蛋白。这些结果表明，病毒衣壳蛋白单独诱导半胱天冬酶激活，导致衣壳蛋白裂解。我们还提供了证据，表明对 caspase 介导的衣壳裂解具有抗性的 AMDV 突变体在 CrFK 细胞中的病毒产量与亲本病毒 AMDV-G 在 37°C 下产生的病毒产量相比增加了约 3 至 5 倍，但在 31.8°C 下则不然。总的来说，我们的结果表明 caspase 活性在 AMDV 感染中发挥多种作用，衣壳蛋白的裂解可能在调节 AMDV 持续感染中发挥作用。
Aleutian mink disease virus (AMDV) is currently the only known member of the genus Amdovirus in the family Parvoviridae. It is the etiological agent of Aleutian disease of mink. We have previously shown that a small protein with a molecular mass of approximately 26 kDa was present during AMDV infection and following transfection of capsid expression constructs (J. Qiu, F. Cheng, L. R. Burger, and D. Pintel, J. Virol. 80: 654-662, 2006). In this study, we report that the capsid proteins were specifically cleaved at aspartic acid residue 420 (D420) during virus infection, resulting in the previously observed cleavage product. Mutation of a single amino acid residue at D420 abolished the specific cleavage. Expression of the capsid proteins alone in Crandell feline kidney (CrFK) cells reproduced the cleavage of the capsid proteins in virus infection. More importantly, capsid protein expression alone induced active caspases, of which caspase-10 was the most active. Active caspases, in turn, cleaved capsid proteins in vivo. Our results also showed that active caspase-7 specifically cleaved capsid proteins at D420 in vitro. These results suggest that viral capsid proteins alone induce caspase activation, resulting in cleavage of capsid proteins. We also provide evidence that AMDV mutants resistant to caspase-mediated capsid cleavage increased virus production approximately 3-to 5-fold in CrFK cells compared to that produced from the parent virus AMDV-G at 37 degrees C but not at 31.8 degrees C. Collectively, our results indicate that caspase activity plays multiple roles in AMDV infection and that cleavage of the capsid proteins might have a role in regulating persistent infection of AMDV.