Development of Guinea Pig as Mamalian for Influenza Virus Transmission

描述（由申请方提供）：自1997年以来，发生了几次高致病性禽流感的区域性暴发，并报告了数百例人禽流感病例。在几乎所有确诊病例中，受感染者都是通过直接接触病禽感染禽流感的。虽然这种情况仍然相对罕见，但东南亚家禽中高毒力H5 N1流感病毒株的持续存在以及与人类H5 N1感染相关的高死亡率（53%）已引起人们对将发生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。人们对阻止这种传播的障碍还没有很好的了解;因此，很难预测目前流行的禽流感毒株如何或何时能够在人群中传播。为了解决我们理解中的这一差距，我们建议开发豚鼠作为流感病毒传播的哺乳动物模型。为了初步评价豚鼠的流感感染和疾病，描述了一系列采用良好表征的人流感毒株的实验。第二组实验将通过评估人流感病毒在豚鼠之间传播的效率，确定豚鼠是否适合进行传播研究。将审查三种传播方式：接触传播、大液滴传播和气溶胶传播。最后，豚鼠将用于比较几种禽流感病毒和人流感病毒的传播性，以了解病毒及其引起的疾病的特征，需要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.