Effects of obesity on the dynamics of Influenza transmission

肥胖对流感传播动态的影响

• 批准号: 10401917
• 负责人: David Gresham
• 金额: $ 81.11万
• 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/10401917
• 关键词: Address; Affect; Animal Testing; Animals; Avian Influenza; Birds; Body mass index; Cells; China; Country; Data; Disease; Dose; Epidemic; Event; Evolution; Exhalation; 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; Persons; 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; diet-induced obesity; epidemiologic data; flu transmission; genetic variant; high risk; immune function; influenza epidemic; influenza infection; influenza virus strain; influenzavirus; innovation; mortality; novel; obese person; 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.

整体的抽象