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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：
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
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/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

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.

项目总结呼吸道病毒如SARS-CoV-2和流感是导致季节性疾病和可以达到大流行的程度。早期人类对这些病毒的反应是在鼻腔和鼻咽区。定义疾病轨迹的生物标记物对于选择治疗和监控决策。我们假设鼻咽trna图谱可以用来预测症状。呼吸道病毒感染造成的严重程度。我们将应用我们最新开发的RNA测序技术探索人类分子特征和影响疾病轨迹的因素。这些配置文件可以包括宿主tRNA的组成、片段模式和表位转录修饰呼吸道。Aim 1将对鼻咽样本进行tRNA测序，以确定感染特征使用记录有SARS-CoV-2、A型流感和B型流感的储存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。并绘制鼻腔tRNA图谱与病毒感染严重程度之间的关系。因为鼻咽部该地区有大量的免疫细胞，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签名相关联。目标2将开发定量聚合酶链式反应分析基于tRNA的生物标记物。我们开发了一种优化鼻咽样本引物设计的算法根据tRNA测序结果。我们的方法还检测到tRNA修饰部分的变化。我们会进一步发展这种分析方法，使其能够应用于鼻咽拭子样本的快速、常规和经济型tRNA生物标志物分析。这些结果将扩大我们对人类tRNA图谱的洞察力一般情况下，呼吸道病毒病理的生物标志物。