Admin Supplement - Effects of obesity on the dynamics of Influenza transmission

管理补充 - 肥胖对流感传播动态的影响

• 批准号: 10171538
• 负责人: David Gresham
• 金额: $ 16.01万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-10 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10171538
• 关键词: Address; Affect; Animal Testing; Animals; Avian Influenza; Birds; Body mass index; Cells; China; Country; Data; Diet; Disease; Dose; Epidemic; Event; Evolution; Exhalation; Expression Profiling; Family suidae; Ferrets; Gene Expression; Goals; Health; Human; Immune response; Individual; Infection; Influenza; Influenza A Virus, H7N9 Subtype; Influenza A Virus, H9N2 Subtype; Innate Immune Response; Integration Host Factors; Knowledge; Longitudinal Studies; Modeling; Molecular; Morbidity - disease rate; Mutation; Non obese; Nose; Obese Mice; Obesity; Overweight; Patients; Population; Populations at Risk; Predisposition; Public Health; RNA Viruses; Reporting; Research Personnel; Risk Factors; Role; Sampling; Severity of illness; Structure; Testing; Thinness; Time; Translating; Underweight; Vaccinated; Vaccination; Vaccines; Viral; Viral Respiratory Tract Infection; Viral reservoir; Virus; Virus Shedding; Weight; Work; World Health Organization; adult obesity; base; cohort; deep sequencing; epidemiologic data; flu transmission; genetic variant; high risk; immune function; influenza epidemic; influenzavirus; innovation; mortality; novel; pressure; response; tool; transmission process; vaccine effectiveness; vaccine efficacy; vaccine response; viral transmission; virus host interaction

OVERALL ABSTRACT We, and others have shown that obesity is an independent risk factor for developing severe influenza infection. However, the impact goes beyond disease severity. Viral clearance is impacted leading to prolonged viral shedding. Vaccine efficacy is reduced and a recent study showed that overweight/obese adults shed influenza virus 102% longer than average weight people. Using our newly developed diet-induced obese (DIO) ferret model we now show that obesity impacts influenza transmission. An avian H9N2 virus that does not transmit via airborne droplets in lean ferrets transmits in 100% of obese animals tested. These findings have dramatic ramifications considering that the World Health Organization (WHO) predicts that most of the world’s population lives in countries where being overweight and obese is more prevalent than being underweight. Our overall goal is to determine how obesity impacts influenza virus transmission. We will determine whether enhanced transmission is due to changes in the virus, to increased susceptibility of the obese host, or to a combination of both, answering questions on whether the virus evolves differently in the obese host as compared to the lean host. Finally, we will explore whether vaccination protects lean and obese hosts. We hypothesize that obese hosts, who have reduced immune function, may be acting as reservoirs for viruses, allowing them to efficiently adapt to the new host and form genetic variants that can potentially be more easily transmitted. Our proposed studies will fill a gap in knowledge by being the first work aimed at also understanding host factors involved in transmission and the role of vaccination in stopping these events. To accomplish our goal, we have proposed the following three interconnected but independent specific aims that will address host-virus interactions: 1. Characterize virus diversity and quantify the dynamics of transmission. 2. Explore vaccine-based protection in the obese host and its effect on transmission. 3. Determine host susceptibility to influenza infection in the obese host. We are uniquely suited to undertake this work given our combined expertise in influenza evolution and transmission dynamics by deep sequencing, and impact of obesity on influenza disease severity and vaccine responses. In addition to the obese ferret model, we have developed innovative tools to define the host response in ferrets that will be invaluable to many investigators. Finally, we have access to longitudinal nasal washes from influenza-infected human cohorts with corresponding body-mass index (BMI) data allowing us to begin translating our findings to human health. In the long term, these studies may reveal critical new information on the public health impact of obesity on influenza infection, transmission, and vaccine protection. Information that is likely to extend beyond influenza.

总体抽象 我们和其他人表明，肥胖是发展严重影响力感染的独立危险因素。 但是，影响超出了疾病的严重程度。病毒清除受到影响，导致病毒延长 脱落。疫苗效率降低，最近的一项研究表明，超重/肥胖的成年人脱落 流感病毒比平均体重人长102％。使用我们新开发的饮食引起的肥胖 （DIO）雪貂模型现在表明肥胖会影响影响扎的传播。一种鸟类H9N2病毒 不会在100％测试的肥胖动物中通过空中液滴在瘦雪貂中传播。这些 发现世界卫生组织（WHO）预测大多数人的发现，发现了巨大的后果 世界人口中的人口生活在超重和肥胖的国家中比成为 体重不足。 我们的总体目标是确定肥胖的影响如何影响病毒传播。我们将确定 增强的传播是由于病毒的变化，增加肥胖宿主的敏感性还是 结合两者的结合，回答有关该病毒在肥胖宿主中是否有不同演变的问题 与精益主机相比。最后，我们将探索疫苗接种是否保护瘦肉和肥胖的宿主。我们 假设降低免疫功能的肥胖宿主可能是病毒的储层， 允许他们有效适应新宿主并形成遗传变异，这些变体可能更容易变得更容易 传输。我们提出的研究将通过成为针对的第一项工作，以填补知识的空白 了解传播涉及的宿主因素以及疫苗接种在停止这些事件中的作用。 为了实现我们的目标，我们提出了以下三个相互联系但独立的特定目标 这将解决主机病毒交互： 1。表征病毒多样性并量化传播动力学。 2。探索肥胖宿主中基于疫苗的保护及其对传播的影响。 3。确定肥胖宿主影响影响力感染的宿主敏感性。 鉴于我们在影响力进化和 通过深度测序传播动力学，肥胖对影响扎病严重程度和疫苗的影响 回答。除了肥胖的雪貂模型外，我们还开发了创新的工具来定义主机 雪貂的反应对许多研究人员来说会很有趣。最后，我们可以使用纵向鼻 用相应的身体质量指数（BMI）数据从影响力的人类人群中洗涤，使我们能够 开始将我们的发现转化为人类健康。从长远来看，这些研究可能揭示了关键的新 有关肥胖对影响力感染，传播和疫苗保护的公共卫生影响的信息。 可能超出影响力的信息。