Restriction of vaccinia virus replication by a ced-3 and ced-4-dependent pathway in Caenorhabditis elegans
Restriction of vaccinia virus replication by a ced-3 and ced-4-dependent pathway in Caenorhabditis elegans
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DOI：
10.1073/pnas.0506442103
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发表时间：
2006-03-14
影响因子：
11.1
通讯作者：
Liao, CL
中科院分区：
文献类型：
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作者：
Liu, WH;Lin, YL;Liao, CL
秀丽隐杆线虫的遗传可塑性和易操作性使其成为研究宿主-病原体相互作用的良好模型。在实验室条件下，许多不同的细菌物种可以致病性地感染线虫，并且所有这些微生物都是线虫的胞外病原体。另一方面，病毒是专性的细胞内寄生虫，但还没有关于线虫病毒感染的报道。我们建立了一个程序，允许牛痘病毒进入并随后在线虫中复制。ced-3、ced-4、ced 9（gf）和egl-1（If）突变体中的病毒复制显著增强，表明核心程序性细胞死亡（PCD）基因ced-3、ced-4、ced-9和egl-1控制线虫中的牛痘病毒复制。ced-3和ced-4等位基因限制病毒复制的能力与它们的细胞杀伤活性相关。此外，在PCD缺陷型突变体中，牛痘病毒复制水平的增加不太可能是由额外的活细胞引起的，因为icd-1过表达对PCD的抑制以及cul-1或lin-23突变体中额外细胞分裂后额外细胞的存在对牛痘病毒复制都没有任何显著影响。因此，核心PCD基因具有独特的功能，在控制牛痘病毒复制在线虫。
Genetic tractability and easy manipulation make Caenorhabditis elegans a good model to study host-pathogen interactions. Dozens of different bacterial species can pathogenically infect C elegans under laboratory conditions, and all of these microbes are extracellular pathogens to nematodes. Viruses, on the other hand, are obligate intracellular parasites, and yet no viral infections have been reported for C elegans. We established a procedure allowing vaccinia virus to enter and subsequently replicate in C elegans. Virus replication was significantly enhanced in ced-3, ced-4, ced9(gf), and egl-1(If) mutants, demonstrating that the core programmed cell death (PCD) genes ced-3, ced-4, ced-9, and egl-1 control vaccinia virus replication in C elegans. The ability of ced-3 and ced-4 alleles to restrict virus replication is correlated with their cell-killing activities. Moreover, the increase in vaccinia virus replication levels in the PCD-defective mutants was not likely to be caused by the extra live cells, as neither the inhibition of PCD by icd-1 overexpression nor the presence of extra cells after extra cell divisions in cul-1 or lin-23 mutants had any significant effect on vaccinia virus replication. Therefore, the core PCD genes possess a unique function in controlling vaccinia virus replication in C elegans.