PIWIL4 and piRNAs in RSV Infection

项目摘要/摘要 急性呼吸道感染是全世界儿童发病和死亡的主要原因。 呼吸道合胞病毒(RSV)是引起儿童、老年人和老年人下呼吸道感染的主要原因 免疫功能受损的患者，以及哮喘恶化的患者。目前尚无有效的RSV治疗方法或疫苗 和许多关于RSV诱导的肺的发病机制的基本问题 疾病尚未得到解答。已发现小的非编码RNA(SncRNAs)调节许多 细胞过程，包括宿主与病毒的相互作用。呼吸道合胞病毒感染可显著改变表达谱 以及几种类型的SncRNAs，如miRNA和TRFs，已经被证明发挥了 在RSV复制和病毒诱导的宿主反应中发挥重要作用。在最近的研究中，我们发现RSV 感染改变了piwi RNAs(PiRNAs)的表达，piRNAs是最大的SncRNA分子之一 在动物细胞中表达。尽管piRNAs的作用最初仅限于性腺发育，但最近 研究已经确定了来自多个器官和细胞类型的piRNAs的特定表达谱，以及不同的 个人资料与几种疾病有关，包括各种癌症、心血管疾病 疾病、自身免疫性和神经退行性疾病。令人惊讶的是，几乎什么都不知道 病毒感染背景下的pIRNA生成/功能和pIWI蛋白。花纹的识别和 人类SncRNAs生成的细节大大有助于理解它们是如何调节宿主的 在病毒感染的背景下的反应。拟议研究的结果将带来新的知识 关于piRNAs在RSV诱导的细胞反应中的作用，潜在地发现新的治疗方法 疾病诊断和预后的靶标和/或生物标记物。

PROJECT SUMMARY/ABSTRACT Acute respiratory tract infections are a leading cause of morbidity and mortality in children worldwide. Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in children, elderly and immunocompromised patients, as well as of asthma exacerbations. No effective treatment or vaccine for RSV is currently available, and many fundamental questions regarding the pathogenesis of RSV-induced lung disease have yet to be answered. Small non-coding RNAs (sncRNAs) have been found to regulate many cellular processes, including host-virus interactions. RSV infection can significantly alter the expression profile of host sncRNAs, and several types of sncRNAs, such as miRNA and tRFs, have been shown to play a significant role in RSV replication and virus-induced host responses. In recent studies, we found that RSV infection alters the expression of piwi RNAs, (piRNAs), one of the largest classes of sncRNA molecules expressed in animal cells. Although the role of piRNAs was initially confined to gonad development, recent studies have identified specific expression profile of piRNAs from multiple organs and cell types, and different profiles have been associated with several diseases, including various types of cancers, cardiovascular diseases, autoimmune and neurodegenerative disorders. Surprisingly, almost nothing is known regarding piRNA generation/function and PIWI proteins in the context of viral infections. Identification of patterns and details of human sncRNAs generation has significantly helped understanding how they modulate host responses in the context of viral infections. The outcome of the proposed studies will lead to new knowledge regarding the role of piRNAs in RSV-induced cellular responses, potentially identifying novel therapeutic targets and/or bio-markers for disease diagnosis and prognosis.