Nasal RNA response to respiratory viral infections

鼻 RNA 对呼吸道病毒感染的反应

基本信息

批准号：
10431323
负责人：
TAO PAN
金额：
$ 26.49万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
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/10431323
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 Epidemic Foundations Future Genetic Genetic Transcription 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 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 Severities Severity of illness Shapes Source Specimen Structure Symptoms Technology Time Transfer RNA Upper respiratory tract Viral Viral Genome Viral Pathogenesis Viral Respiratory Tract Infection Virus Virus Diseases base clinical care clinical diagnostics comparative design epitranscriptomics high reward high risk influenzavirus insight medical schools mortality nasopharyngeal swab non-genetic novel pandemic disease pathogen pathogenic virus public health emergency respiratory respiratory infection virus respiratory virus response therapeutic development transcriptome sequencing

项目摘要

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.

项目概要 SARS-CoV-2 和流感等呼吸道病毒是引起季节性疾病和流感的常见病原体。可能达到大流行的程度。人类对这些病毒的早期反应是在鼻腔和鼻咽区域。定义疾病轨迹的生物标志物对于选择治疗和选择非常重要监督决策。我们假设鼻咽 tRNA 谱可用于预测症状呼吸道病毒感染引起的严重程度。我们将应用我们新开发的RNA测序技术探索导致疾病轨迹的人类分子特征和因素。这些配置文件可以包括上层的宿主 tRNA 组成、片段化模式和表观转录组修饰呼吸道。目标 1 对鼻咽样本进行 tRNA 测序，以识别感染特征使用已记录有 SARS-CoV-2、甲型流感和乙型流感的鼻咽拭子检测宿主 tRNA 感染。结合已知的患者结果，我们将剖析鼻咽拭子中的 tRNA 特征并绘制鼻 tRNA 谱与病毒感染严重程度之间的关系。自从鼻咽部该区域充满了免疫细胞，包括对抗病毒感染的秘密核糖核酸酶，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。目标 2 将开发 qPCR 检测基于 tRNA 的生物标志物。我们开发了一种优化鼻咽样本引物设计的算法基于 tRNA 测序结果。我们的方法还检测 tRNA 修饰分数的变化。我们将进一步开发该测定法，使其能够应用于鼻咽拭子样本，以进行快速、常规和经济 tRNA 生物标志物分析。这些结果将扩展我们对人类 tRNA 图谱如何进行分析的见解一般呼吸道病毒病理学的生物标志物。