Mechanisms of Influenza a Virus Transmission in Ferretts

甲型流感病毒在雪貂中的传播机制

• 批准号: 7687330
• 负责人: DANIEL R PEREZ
• 金额: $ 10万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-31 至 2009-07-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7687330
• 关键词: Mechanisms; Influenza; Virus; Transmission; Ferretts

DESCRIPTION (provided by applicant): Our long term goal is to establish animal models for human influenza infection, pathogenesis, transmission and evolution. There is particular concern about the possibility that avian influenza viruses of the H5N1 subtype could lead to a pandemic. These viruses are transmitting directly from birds to humans, although they have been unable yet to maintain sustained human-to-human transmission. We propose to study the mechanisms that avian influenza viruses require to infect mammals as well as the potential evolution of those viruses to transmit human-to-human which is required to cause a pandemic. The molecular basis for the efficient transmission of influenza viruses from among humans is not well understood, although the aerosol transmission is known to be important in the process. With the emergence of direct transmission of influenza viruses from avian species to humans but little human-to-human transmission, it is crucial to determine the genetic traits that lead to efficient transmission of potentially pandemic viruses in humans. We propose two specific aims to address: 1) The transmissibility potential of human H1, H2, and H3 viruses as well as avian H5, H7, and H9 viruses that have been implicated in bird-to-human infections. We will determine the effect of particle size for efficient aerosol spread and the effect that virus morphology has to establish a natural chain of transmission in the ferret model. We will compare the effect of influenza infections in two animal model systems, the ferret and the cotton rat, both of which can display typical flu symptoms without requiring virus adaptation. We will use unrestrained whole body plethysmography to determine the frequency of respiration, airway responsiveness (ratio of inspiration to expiration) and time between breaths and compare them with the effect of aerosolization of influenza virus particles. We will study virus survival in sputum samples of infected ferrets to better understand the natural conditions that might affect the stability of the virus and its effect for efficient transmission. 2) We will generate avian/human reassortant influenza viruses by reverse genetics or by co-infection of ferrets with an avian and a human strain to determine whether such reassortants are viable and better define the factors that control transmission of avian influenza viruses in this animal model system.

描述(申请人提供)：我们的长期目标是建立人类流感感染、发病机制、传播和进化的动物模型。特别令人担忧的是，H5N1亚型禽流感病毒可能导致大流行。这些病毒正在从禽类直接传播给人类，尽管它们还无法维持持续的人与人之间的传播。我们建议研究禽流感病毒感染哺乳动物所需的机制，以及这些病毒在人与人之间传播的潜在进化，这是导致大流行所必需的。流感病毒在人与人之间有效传播的分子基础还不是很清楚，尽管已知气溶胶传播在这一过程中很重要。随着禽流感病毒从禽类直接传播到人类，但人与人之间的传播很少，确定导致潜在大流行病毒在人类中有效传播的遗传特征至关重要。我们提出了两个具体的目标来解决：1)人类H1、H2和H3病毒以及与禽类到人的感染有关的禽类H5、H7和H9病毒的传播潜力。我们将在雪貂模型中确定颗粒大小对有效气溶胶传播的影响，以及病毒形态对建立自然传播链的影响。我们将比较两个动物模型系统--雪貂和棉鼠--感染流感的效果，这两个系统都可以在不需要病毒适应的情况下表现出典型的流感症状。我们将使用自由全身体积描记仪来确定呼吸频率、呼吸道反应性(吸气与呼气的比率)和呼吸间隔时间，并将它们与流感病毒颗粒雾化的效果进行比较。我们将研究病毒在受感染雪貂的唾液样本中的存活情况，以更好地了解可能影响病毒稳定性的自然条件及其对有效传播的影响。2)我们将通过反向遗传学或通过雪貂与禽类和人类毒株的混合感染来产生禽流感病毒，以确定这种重组病毒是否可行，并更好地确定在这个动物模型系统中控制禽流感病毒传播的因素。