基于热休克同源蛋白70的miRNA调控网络的建立及其在WSSV侵染宿主过程的功能和机制研究

Virus-encoded and cellular miRNAs widely participate physiology function and activities between virus and host, however, the function and mechanism of miRNA involved in WSSV infection are rarely known. Our previous studies showed shrimp Heat shock protein Hsc70 play key roles in WSSV infection, immune evasion, host cell apoptosis and virus package. We also found that Hsc70 was significantly regulated by both WSSV-encoded and shrimp cellular miRNAs in the shrimp primary cells. In this study, we are trying to systematically identify the WSSV-encoded and shrimp cellular miRNAs that are targeting or regulated by shrimp hsc70, so that to establish the hsc70 centred miRNA network and explore the miRNA's function during WSSV infection, immune evasion and virus package.. Meanwhile, we will perform a detailed study of the mechanism that miRNAs regulate critical gene Hsc70. All these studies, may contribute to the fully comprehension of the complicate WSSV life cycle, and have significant meaning for exploring the molecular mechanism of WSSV outbreak and disease control.

病毒和宿主的编码的microRNA广泛参与着病毒和宿主之间的各种生理功能和活动，然而对于miRNA在白斑病毒WSSV侵染宿主过程中的功能和机制我们还所知甚少。我们之前的研究表明热休克同源蛋白70（Hsc70）在WSSV感染宿主、逃避宿主免疫、介导宿主细胞凋亡和病毒粒子包装等过程中起关键作用；而Hsc70在对虾卵巢原代细胞中也受到来自宿主和病毒自身编码miRNA的调控。本课题拟通过系统鉴定靶向调控以及受对虾hsc70调控的病毒和宿主编码的miRNA，建立以对虾hsc70为中心的病毒及宿主编码miRNA调控网络，研究这些miRNA对病毒感染、包装、免疫逃逸等重要生命活动的影响。同时探究病毒及宿主编码miRNA通过调控感染关键基因hsc70参与WSSV对宿主侵染的分子机制。这将有助于充分了解WSSV复杂的生命周期，对于探索WSSV暴发流行的分子机制和对虾病害防治新途径都具有重要意义。

病毒和宿主的编码的microRNA 广泛参与着病毒和宿主之间的各种生理功能和活动，然而对于miRNA 在白斑病毒WSSV 侵染宿主过程中的功能和机制我们还所知甚少。我们之前的研究表明热休克同源蛋白70（Hsc70）在WSSV 感染宿主、逃避宿主免疫、介导宿主细胞凋亡和病毒粒子包装等过程中起关键作用；而Hsc70也受到来自宿主和病毒自身编码miRNA 的调控。本课题从WSSV侵染宿主过程出现差异性表达的miRNA中系统鉴定了3个靶向调控Hsc70的miRNA和5个受Hsc70 调控的miRNA，从而建立起以Hsc70 为中心的miRNA 调控网络，并深入验证了其中效果最显著的宿主miR-9a在WSSV侵染宿主细胞过程中的表达变化，阐明了miR-9a对Hsc70的靶向调控分子机制，揭示了miR-9a通过下调Hsc70的表达增强宿主细胞抗病毒凋亡效应，从而抑制WSSV对宿主细胞侵染的效应机制。这些发现将有助于充分了解WSSV 复杂的生命周期，对于探索WSSV 暴发流行的分子机制和对虾病害防治新途径都具有重要意义。