Key Laboratory of Conservation Biology for Endangered Wildlife of the Ministry of Education, Key Laboratory of Animal Virology of Ministry of Agriculture and College of Life Sciences, Zhejiang University, Hangzhou, China.
RNA Biol. 2012 Jul;9(7):1019-29. doi: 10.4161/rna.20741. Epub 2012 Jul 1.
Guided by miRNAs, RNAi plays an important role in virus-host interactions by fine-tuning gene expression. Many viral and cellular miRNAs are involved in virus infection, though no comprehensive general model for miRNAs derived from invertebrate DNA viruses exists for their function in eukaryotic systems, despite extensive research on miRNAs. To address this issue, the miRNAs from shrimp white spot syndrome virus (WSSV), a DNA virus with a 305 kb double-stranded circular DNA genome, were characterized. Based on WSSV miRNA microarray and northern blot analyses, WSSV was shown to possess the capacity to encode 40 distinct viral miRNAs, a miRNA content roughly 360 times greater than that of humans. These findings suggested that the high content of viral miRNAs might greatly contribute to viral variability in response selective pressures in the host environment. Transcription analysis revealed that 80% of WSSV miRNAs were expressed during early stages of viral infection, indicating their importance in initial infective processes. Additionally, biogenesis of viral miRNAs was demonstrated to be dependent on host Drosha and Dicer 1, mediated by Ago 1, and viral miRNAs, including WSSV-miR211 and WSSV-miR212, were required for successful WSSV infection. During WSSV infection, numerous viral genes were likely targeted by WSSV miRNAs. The current study presented the first comprehensive view of viral miRNAs encoded by an invertebrate DNA virus, providing insight into the molecular events of virus-host interactions.
在 miRNA 的指导下,RNAi 通过精细调控基因表达在病毒-宿主相互作用中发挥重要作用。许多病毒和细胞 miRNA 参与病毒感染,尽管在真核系统中对 miRNA 的功能进行了广泛研究,但仍没有关于无脊椎动物 DNA 病毒衍生的 miRNA 的综合通用模型。为了解决这个问题,对虾白斑综合征病毒(WSSV)的 miRNA 进行了表征,WSSV 是一种具有 305 kb 双链环状 DNA 基因组的 DNA 病毒。基于 WSSV miRNA 微阵列和 northern blot 分析,表明 WSSV 具有编码 40 种不同病毒 miRNA 的能力,miRNA 含量大约是人类的 360 倍。这些发现表明,高含量的病毒 miRNA 可能极大地促进了病毒在宿主环境中选择性压力下的变异性。转录分析显示,80%的 WSSV miRNA 在病毒感染的早期阶段表达,表明它们在初始感染过程中的重要性。此外,病毒 miRNA 的生物发生被证明依赖于宿主 Drosha 和 Dicer 1,由 Ago 1 介导,并且病毒 miRNA,包括 WSSV-miR211 和 WSSV-miR212,是成功感染 WSSV 所必需的。在 WSSV 感染期间,许多病毒基因可能是 WSSV miRNA 的靶标。本研究首次全面描述了无脊椎动物 DNA 病毒编码的病毒 miRNA,为病毒-宿主相互作用的分子事件提供了深入了解。