PIWIL4 and piRNAs in RSV Infection

RSV 感染中的 PIWIL4 和 piRNA

基本信息

批准号：
10667951
负责人：
Antonella Casola
金额：
$ 24万
依托单位：
UNIVERSITY OF TEXAS MED BR GALVESTON
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-01-25 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10667951
关键词：
Acute Affect Airway Disease Animals Aubergine Autoimmune Diseases Bacterial Pneumonia Biogenesis Biological Process Bronchiolitis Candidate Disease Gene Cardiovascular Diseases Categories Cell Line Cell Separation Cell physiology Cells Cessation of life Child Clinical Complex Conserved Sequence Cytoplasm DNA Defense Mechanisms Developing Countries Disease Elderly Epigenetic Process Epithelial Cells Family Gene Expression Gene Expression Regulation Gene Targeting Generations Genetic Transcription Germ Cells Germ Lines Homologous Gene Host Defense Human Immune Immune response Immunity Immunocompromised Host Infection Inflammatory Response Innate Immune Response Investigation Knowledge Licensing Life Link Literature Location Lower Respiratory Tract Infection Lung Lung diseases Messenger RNA Methods MicroRNAs Modeling Molecular Molecular Target Morbidity - disease rate Mus Neurodegenerative Disorders Nuclear Organ Organelles Other Genetics Outcome Pathogenesis Pathway interactions Pattern Play Pneumonia Property Proteins Public Health RNA RNA Binding RNA Interference RNA analysis Respiratory Syncytial Virus Infections Respiratory Syncytial Virus Vaccines Respiratory Tract Infections Respiratory syncytial virus Retrotransposon Role Signal Transduction Small Interfering RNA Small Nucleolar RNA Small RNA Somatic Cell Spermatogenesis Subcellular structure Syndrome Testing Therapeutic Transcriptional Regulation Untranslated RNA Vaccines Viral Virus Virus Diseases Virus Replication airway epithelium antagonist asthma exacerbation cancer type cell type circular RNA disease diagnosis disease prognosis effective therapy epigenetic regulation exosome flu genetic element gonad development information gathering loss of function member mortality mouse model new therapeutic target novel older patient pathogen pediatric patients pharmacologic physical property piRNA prevent protein complex respiratory morbidity respiratory pathogen response therapeutic biomarker therapeutic target transcriptome virus host interaction

项目摘要

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.

项目概要/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）是儿童、老年人和儿童下呼吸道感染的主要原因。免疫功能低下的患者以及哮喘恶化的患者。 RSV 没有有效的治疗方法或疫苗目前，有关 RSV 引起的肺病发病机制的许多基本问题已得到解决。疾病尚未得到解答。小非编码 RNA (sncRNA) 被发现可以调节许多细胞过程，包括宿主与病毒的相互作用。 RSV 感染可显着改变表达谱宿主 sncRNA 以及几种类型的 sncRNA（例如 miRNA 和 tRF）已被证明发挥着重要作用在 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 piwi RNA（piRNA）的表达，piwi RNA 是最大的 sncRNA 分子类别之一在动物细胞中表达。尽管 piRNA 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 piRNA 的特定表达谱，以及不同的谱与多种疾病相关，包括各种类型的癌症、心血管疾病疾病、自身免疫性疾病和神经退行性疾病。令人惊讶的是，人们对此几乎一无所知病毒感染背景下的 piRNA 生成/功能和 PIWI 蛋白。模式识别和人类 sncRNA 生成的细节有助于理解它们如何调节宿主病毒感染情况下的反应。拟议研究的结果将带来新的知识关于 piRNA 在 RSV 诱导的细胞反应中的作用，可能确定新的治疗方法用于疾病诊断和预后的靶标和/或生物标志物。