Development of Guinea Pig as Mamalian for Influenza Virus Transmission

描述(申请人提供)：自1997年以来，发生了几次高致病性禽流感的地区性暴发，并报告了数百例人感染禽流感病例。在几乎所有确诊病例中，感染者通过与患病家禽直接接触感染禽流感。尽管此类事件仍然相对罕见，但东南亚家禽中持续存在高毒力的H5N1流感毒株，以及与人类感染H5N1相关的高死亡率(53%)，已引起人们对将发展一场特别致命的流感大流行的担忧。要做到这一点，仍需满足一个标准：大流行性流感必须在人与人之间有效传播。防止这种传播的障碍还不是很清楚；因此，很难预测目前流行的禽流感毒株将如何或何时能够在人类群体中传播。为了解决我们理解中的这一差距，我们建议将豚鼠作为流感病毒传播的哺乳动物模型。为了初步评估豚鼠的流感感染和疾病，描述了使用具有良好特征的人类流感毒株的一系列实验。第二组实验将通过评估人类流感病毒在这些动物之间的传播效率，特别是确定豚鼠是否适合进行传播研究。将研究三种传播模式：接触传播、大液滴传播和气溶胶传播。最后，将用豚鼠比较几种禽流感病毒和人类流感病毒的传播性，以了解病毒及其引起的疾病的哪些特征才能支持哺乳动物宿主之间的传播。

DESCRIPTION (provided by applicant): Since 1997 several regional outbreaks of highly pathogenic avian influenza have occurred, and hundreds of cases of avian influenza in humans have been reported. In nearly all confirmed cases, infected persons contracted avian influenza through direct contact with diseased poultry. Although such occurrences remain relatively rare, the persistence of highly virulent H5N1 influenza strains among poultry in Southeast Asia and the high fatality rate (53%) associated with H5N1 infection of humans have engendered concern that a particularly deadly influenza pandemic will develop. For this to occur, one criterion remains to be fulfilled: pandemic influenza must be efficiently transmitted from person-to-person. The barrier preventing such transmission is not well understood; thus, it is difficult to predict how or when currently circulating strains of avian influenza will become competent for propagation within the human population. To address this gap in our understanding, we propose the development of the guinea pig as a mammalian model for influenza virus transmission. For the initial evaluation of influenza infection and disease in guinea pigs, a series of experiments employing well-characterized strains of human influenza are described. A second set of experiments will establish the suitability of guinea pigs for transmission studies in particular, by assessing the efficiency of spread of human influenza viruses between these animals. Three modes of transmission will be examined: contact-, large droplet- and aerosol-based spread. Finally, guinea pigs will be used to compare the transmissibility of several avian and human influenza viruses toward the aim of understanding what characteristics of the virus, and of the disease it causes, are required to support transmission among mammalian hosts.