Department of Microbiology and Immunology, University of California, San Francisco, California, USA.
Nat Struct Mol Biol. 2010 May;17(5):547-54. doi: 10.1038/nsmb.1810. Epub 2010 Apr 18.
Insect viruses have evolved strategies to control the host RNAi antiviral defense mechanism. In nature, Drosophila melanogaster C virus (DCV) infection causes low mortality and persistent infection, whereas the closely related cricket paralysis virus (CrPV) causes a lethal infection. We show that these viruses use different strategies to modulate the host RNAi defense machinery. The DCV RNAi suppressor (DCV-1A) binds to long double-stranded RNA and prevents processing by Dicer2. In contrast, the CrPV suppressor (CrPV-1A) interacts with the endonuclease Argonaute 2 (Ago2) and inhibits its activity without affecting the microRNA (miRNA)-Ago1-mediated silencing. We examined the link between viral RNAi suppressors and the outcome of infection using recombinant Sindbis viruses encoding either CrPV-1A or DCV-1A. Flies infected with Sindbis virus expressing CrPV-1A showed a marked increase in virus production, spread and mortality. In contrast, Sindbis pathogenesis was only modestly increased by expression of DCV- 1A. We conclude that RNAi suppressors function as virulence factors in insects and can target the Drosophila RNAi pathway at different points.
昆虫病毒已经进化出了控制宿主 RNAi 抗病毒防御机制的策略。在自然界中，黑腹果蝇 C 病毒（DCV）感染会导致低死亡率和持续性感染，而与之密切相关的蟋蟀麻痹病毒（CrPV）则会导致致命感染。我们表明，这些病毒使用不同的策略来调节宿主的 RNAi 防御机制。DCV 的 RNAi 抑制剂（DCV-1A）与长双链 RNA 结合，阻止 Dicer2 的加工。相比之下，CrPV 的抑制剂（CrPV-1A）与核酸内切酶 Argonaute 2（Ago2）相互作用，抑制其活性，而不影响 miRNA（miRNA）-Ago1 介导的沉默。我们使用编码 CrPV-1A 或 DCV-1A 的重组辛德毕斯病毒来研究病毒 RNAi 抑制剂与感染结果之间的联系。感染表达 CrPV-1A 的辛德毕斯病毒的果蝇显示出病毒产量、传播和死亡率的显著增加。相比之下，表达 DCV-1A 仅适度增加了辛德毕斯病的发病机制。我们得出结论，RNAi 抑制剂在昆虫中作为毒力因子发挥作用，可以针对不同的点靶向果蝇的 RNAi 途径。
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