Nasal RNA response to respiratory viral infections

鼻 RNA 对呼吸道病毒感染的反应

• 批准号: 10598579
• 负责人: TAO PAN
• 金额: $ 20.79万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10598579
• 关键词: 2019-nCoV; Age; Algorithms; Biological Assay; Biological Factors; Biological Markers; COVID-19; COVID-19 diagnosis; COVID-19 patient; Cells; Data; Diagnostic tests; Disease; Disease Outcome; Economics; Environment; Foundations; Future; Genetic; Goals; Health; Human; Immune; Immune response; Immunomodulators; Individual; Infection; Influenza; Influenza A virus; Influenza B Virus; Innate Immune Response; Intervention; Life Style; Ligation; Link; Maps; Metabolism; Modification; Molecular Diagnostic Testing; Molecular Profiling; Monitor; Morbidity - disease rate; Nasal cavity; Nasopharynx; Nose; Nucleic Acids; Oral cavity; Pathology; Patient Care; Patient-Focused Outcomes; Patients; Pattern; Predictive Factor; Protein Biosynthesis; RNA; Research; Resources; Respiratory Disease; Respiratory Tract Infections; Ribonucleases; Sampling; Seasons; Severities; Severity of illness; Shapes; Source; Specimen; Structure; Symptoms; Technology; Time; Transfer RNA; Upper respiratory tract; Viral Genome; Viral Pathogenesis; Viral Respiratory Tract Infection; Virus; Virus Diseases; clinical care; clinical diagnostics; comparative; design; epitranscriptomics; future epidemic; future pandemic; high reward; high risk; influenzavirus; insight; medical schools; mortality; nasopharyngeal swab; non-genetic; novel; pandemic disease; pathogen; pathogenic virus; posttranscriptional; public health emergency; respiratory; respiratory infection virus; respiratory virus; response; therapeutic development; transcriptome sequencing; viral pandemic

PROJECT SUMMARY Respiratory viruses such as SARS-CoV-2 and influenza are common pathogens that cause seasonal illness and can reach pandemic proportions. The early human response to these viruses are in the nasal cavity and nasopharyngeal regions. Defining biomarkers of disease trajectory is important for opting for treatment and monitoring decisions. We hypothesize that the nasopharyngeal tRNA profiles can be used to predict symptom severity resulting from respiratory virus infection. We will apply our newly developed RNA sequencing technology to explore the human molecular signatures and factors that contribute to disease trajectory. These profiles can include the host tRNA composition, fragmentation patterns, and epitranscriptomic modification in the upper respiratory tract. Aim 1 will perform tRNA sequencing of nasopharyngeal samples to identify infection signatures of host tRNA using banked nasopharyngeal swabs with documented SARS-CoV-2, influenza A, and influenza B infections. Together with known patient outcomes, we will dissect tRNA signatures in nasopharyngeal swabs and map the relationship between nasal tRNA profiles and viral infection severity. Since the nasopharyngeal region is highly populated with immune cells, including secret RNases to counter viral infections, we will quantify the ribonuclease activity and associate these results with tRNA signatures. Aim 2 will develop qPCR assays of tRNA-based biomarkers. We developed an algorithm that optimizes primer design for nasopharyngeal samples based on tRNA sequencing results. Our approach also detects changes in tRNA modification fractions. We will further develop this assay to enable its implementation to nasopharyngeal swab samples for rapid, routine and economic tRNA biomarker analysis. These results will expand our insights on how human tRNA profiles can be biomarkers for the pathology of respiratory viruses in general.

项目摘要 SARS-COV-2和流感等呼吸道病毒是引起季节性疾病和的常见病原体 可以达到大流行比例。对这些病毒的早期人类反应是在鼻腔中 鼻咽区域。定义疾病轨迹的生物标志物对于选择治疗和 监视决策。我们假设鼻咽tRNA特征可用于预测症状 呼吸道病毒感染引起的严重程度。我们将应用新开发的RNA测序技术 探索人的分子特征和导致疾病轨迹的因素。这些轮廓可以 在上部包括宿主tRNA组成，片段化模式和表面参考的修饰 呼吸道。 AIM 1将执行鼻咽样品的tRNA测序以识别感染特征 使用储存的鼻咽拭子，带有记录的SARS-COV-2，流感和流感B的宿主tRNA 感染。与已知的患者结局一起，我们将在鼻咽拭子中剖析tRNA特征 并绘制鼻tRNA谱和病毒感染严重程度之间的关系。自鼻咽 区域被免疫细胞高度填充，包括针对病毒感染的秘密RNass，我们将量化 核糖核酸酶活性并将这些结果与tRNA特征相关联。 AIM 2将开发QPCR测定 基于TRNA的生物标志物。我们开发了一种优化鼻咽样品底漆设计的算法 基于tRNA测序结果。我们的方法还检测到tRNA修饰部分的变化。我们将 进一步开发此测定法，以使其对鼻咽拭子样品实施，以进行快速，常规和 经济tRNA生物标志物分析。这些结果将扩大我们对人类tRNA概况的见解 一般而言，呼吸道病毒病理学的生物标志物。