Effects of obesity on the dynamics of Influenza transmission

肥胖对流感传播动态的影响

基本信息

  • 批准号:
    10624463
  • 负责人:
  • 金额:
    $ 81.01万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-06-10 至 2025-05-31
  • 项目状态:
    未结题

项目摘要

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.
总体摘要 我们和其他人已经表明,肥胖是发展严重流感感染的独立危险因素。 然而,影响超出了疾病的严重程度。病毒清除受到影响,导致病毒 脱落疫苗效力降低,最近的一项研究表明,超重/肥胖的成年人 流感病毒的寿命比平均体重的人长102%。使用我们新开发的饮食诱导肥胖 (DIO)雪貂模型,我们现在表明,肥胖影响流感传播。一种禽类H9 N2病毒, 在瘦雪貂中不通过空气飞沫传播,在测试的肥胖动物中100%传播。这些 考虑到世界卫生组织(WHO)预测, 世界人口的一半生活在超重和肥胖比肥胖更普遍的国家。 体重不足。 我们的总体目标是确定肥胖如何影响流感病毒传播。我们将确定 增强的传播是否是由于病毒的变化,肥胖宿主的易感性增加,或 两者的结合,回答了病毒在肥胖宿主中是否会以不同的方式进化的问题, 相比之下,最后,我们将探讨是否接种疫苗保护瘦和肥胖的主机。我们 假设免疫功能下降的肥胖宿主可能是病毒的宿主, 使它们能够有效地适应新的宿主,并形成遗传变异, 传来我们提出的研究将填补知识的空白,作为第一项工作,旨在也 了解参与传播的宿主因素以及疫苗接种在阻止这些事件中的作用。 为了实现这一目标,我们提出了以下三个相互联系但又相互独立的具体目标 这将解决主机与病毒的相互作用: 1.描述病毒多样性并量化传播动态。 2.探索肥胖宿主中基于疫苗的保护作用及其对传播的影响。 3.确定肥胖宿主对流感感染的易感性。 鉴于我们在流感演变方面的综合专业知识, 深度测序的传播动态,以及肥胖对流感疾病严重程度和疫苗的影响 应答除了肥胖雪貂模型,我们还开发了创新的工具来定义宿主 雪貂的反应对许多研究人员来说将是无价的。最后,我们有机会纵向鼻 来自流感感染人群的洗涤液,以及相应的体重指数(BMI)数据,使我们能够 开始将我们的发现应用于人类健康。从长远来看,这些研究可能会揭示关键的新 关于肥胖对流感感染、传播和疫苗保护的公共卫生影响的信息。 信息可能超越流感。

项目成果

期刊论文数量(10)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
The Nature of Immune Responses to Influenza Vaccination in High-Risk Populations.
  • DOI:
    10.3390/v13061109
  • 发表时间:
    2021-06-09
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Wiggins KB;Smith MA;Schultz-Cherry S
  • 通讯作者:
    Schultz-Cherry S
Efficacy of oseltamivir treatment in influenza virus-infected obese mice.
  • DOI:
    10.1128/mbio.00887-23
  • 发表时间:
    2023-08-31
  • 期刊:
  • 影响因子:
    6.4
  • 作者:
    Honce, Rebekah;Jones, Jeremy;Meliopoulos, Victoria A.;Livingston, Brandi;Sharp, Bridgett;Estrada, Leonardo D.;Wang, Lindsey;Caulfield, William;Freeman, Burgess;Govorkova, Elena;Schultz-Cherry, Stacey
  • 通讯作者:
    Schultz-Cherry, Stacey
Serological Responses to Influenza Vaccination during Pregnancy.
  • DOI:
    10.3390/microorganisms9112305
  • 发表时间:
    2021-11-06
  • 期刊:
  • 影响因子:
    4.5
  • 作者:
    Vazquez-Pagan A;Schultz-Cherry S
  • 通讯作者:
    Schultz-Cherry S
Host obesity impacts genetic variation in influenza A viral populations.
宿主肥胖会影响甲型流感病毒群体的遗传变异。
  • DOI:
    10.1101/2023.07.12.548715
  • 发表时间:
    2023
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Knoll,Marissa;Honce,Rebekah;Meliopoulos,Victoria;Schultz-Cherry,Stacey;Ghedin,Elodie;Gresham,David
  • 通讯作者:
    Gresham,David
Transkingdom Interactions Important for the Pathogenesis of Human Viruses.
跨界相互作用对人类病毒的发病机制很重要。
  • DOI:
    10.1093/infdis/jiaa735
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Nishimoto,Andrew;Wohlgemuth,Nicholas;Rosch,Jason;Schultz-Cherry,Stacey;Cortez,Valerie;Rowe,HannahM
  • 通讯作者:
    Rowe,HannahM
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David Gresham其他文献

David Gresham的其他文献

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{{ truncateString('David Gresham', 18)}}的其他基金

Constraints and Consequences of Copy Number Variation
拷贝数变异的限制和后果
  • 批准号:
    10385824
  • 财政年份:
    2020
  • 资助金额:
    $ 81.01万
  • 项目类别:
Constraints and Consequences of Copy Number Variation
拷贝数变异的限制和后果
  • 批准号:
    10598022
  • 财政年份:
    2020
  • 资助金额:
    $ 81.01万
  • 项目类别:
Constraints and Consequences of Copy Number Variation
拷贝数变异的限制和后果
  • 批准号:
    10155508
  • 财政年份:
    2020
  • 资助金额:
    $ 81.01万
  • 项目类别:
Constraints and Consequences of Copy Number Variation
拷贝数变异的限制和后果
  • 批准号:
    9973827
  • 财政年份:
    2020
  • 资助金额:
    $ 81.01万
  • 项目类别:
The Quantitative Biological Systems Training (QBIST) Program
定量生物系统培训 (QBIST) 计划
  • 批准号:
    10413886
  • 财政年份:
    2019
  • 资助金额:
    $ 81.01万
  • 项目类别:
The Quantitative Biological Systems Training (QBIST) Program
定量生物系统培训 (QBIST) 计划
  • 批准号:
    10176536
  • 财政年份:
    2019
  • 资助金额:
    $ 81.01万
  • 项目类别:
Effects of obesity on the dynamics of Influenza transmission
肥胖对流感传播动态的影响
  • 批准号:
    10163793
  • 财政年份:
    2019
  • 资助金额:
    $ 81.01万
  • 项目类别:
The Quantitative Biological Systems Training (QBIST) Program
定量生物系统培训 (QBIST) 计划
  • 批准号:
    10633120
  • 财政年份:
    2019
  • 资助金额:
    $ 81.01万
  • 项目类别:
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
  • 财政年份:
    2019
  • 资助金额:
    $ 81.01万
  • 项目类别:
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
  • 财政年份:
    2019
  • 资助金额:
    $ 81.01万
  • 项目类别:

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