Combating Swine Influenza Initiative (model project)

30多年来第一次人类流感大流行正在进行中，致病病毒是由两种不同的猪流感病毒结合而成，一种来自美国，另一种来自欧洲。分析表明，这两种祖病毒可能在猪中传播了约9年而未被检测到。流感病毒相互联合收割机产生新病毒的能力以及快速突变的能力是它们在新的哺乳动物物种（包括人类）中传播能力的重要特征。猪比大多数其他动物更容易感染流感病毒，这使得它们成为可能发生这种病毒混合的重要动物。猪流感感染在欧洲的猪中很常见，至少每年在许多农场传播。VLA的实验研究表明，猪可以感染大流行性人类病毒，重要的是，可以将病毒传播给与它们共同饲养的其他猪。由人类大流行病毒引起的猪流感在至少三个国家爆发，可能是养猪户将病毒传染给猪后感染的。在英国，一些猪是在大规模、非常密集的种群中养殖的，如果这些农场感染了大流行性流感病毒，就会产生大量的病毒，给饲养猪的农民带来不可预测的后果。人类大流行性病毒的起源来自猪流感病毒，猪对大流行性病毒的易感性以及世界各地养猪场的感染，在其潜在的“混合容器”作用的背景下，对人类和猪的健康提出了几个直接和重要的问题和挑战。这项赠款，沿着并行的人口赠款申请，旨在回答其中一些问题，并在这样做的过程中，提供一个直接的科学证据基础，为旨在最大限度地减少大流行病对人类和动物的影响的政策提供信息。我们将确定大流行性病毒传播给猪的后果，考虑个体的临床表现，包括导致疾病体征的宿主或“患者”机制，以及病毒的传播。这些研究将考虑到一些猪可能通过先前的“正常”猪流感感染而自然地部分免疫。我们将利用这项工作来估计猪感染大流行病毒对公共卫生可能构成的挑战。我们的详细调查将包括猪流感的基因研究，猪感染“正常”猪和大流行病毒株的免疫学和病毒学研究。我们将研究病毒在猪与猪之间的传播水平，并调查该疾病的临床影响。该项目将大大增加关于猪流感的可用数据量，以便我们能够正确估计这种感染造成的未来风险。通过比较猪研究的数据和大流行性病毒传播时发生的人类病例的数据，我们将能够评估猪作为动物模型是否适合研究大流行性流感对人类的影响。这笔赠款产生的数据将用于研究病毒突变率，并确定与猪和与猪打交道的人之间传播相关的流感病毒的特定突变。这将使我们能够更好地预测大流行性病毒变异后在人和猪中变得更具毒性的直接威胁，特别是如果人类大流行性病毒在猪群中流行的话。

The first human influenza pandemic in more than 30 years is ongoing, with the causative virus having arisen from the combination of two different swine influenza viruses, one originating in the USA and the other in Europe. Analyses have demonstrated that the two progenitor viruses were circulating undetected, probably in pigs, for around 9 years. The ability of influenza viruses to both combine with each other to produce new viruses and also to mutate rapidly are important features in their ability to transmit in novel mammalian species, including humans. Pigs are susceptible to a larger range of influenza viruses than most other animals and this makes them of importance as animals in which such viral mixing can happen. Swine flu infection is common in pigs in Europe and circulates through many farms on at least an annual basis. Experimental studies at VLA have demonstrated that pigs can be infected with the pandemic human virus and, importantly, can spread the virus to other pigs that they are co-housed with. Outbreaks of swine flu in pigs, caused by the human pandemic virus, have occurred in at least three countries, probably following infection of pig farmers who have transmitted the virus to pigs. In Great Britain, some pigs are farmed in large, very dense populations and, should these farms become infected with the pandemic flu virus, large amounts of virus would be produced with unpredictable consequences for the farmers caring for the pigs. The origin of the human pandemic virus from swine flu viruses, the susceptibility of pigs to the pandemic virus and the infection of pig farms around the world, against the background of their potential 'mixing vessel' role, raises several immediate and important questions and challenges for both human and swine health. This grant, along with the parallel population grant application, aims to answer some of them and, in doing so, to provide an immediate scientific evidence base to inform policies aimed at minimising the impact of the pandemic in both humans and animals. We will define the consequences of spread of the pandemic virus to pigs, considering the individual clinical presentation, including the host or 'patient' mechanisms that result in disease signs, and the transmission of the virus. These studies will take into account that some pigs may be naturally partially immune through prior 'normal' swine flu infection. We will use this work to estimate the likely challenge posed to public health by pig infection with the pandemic virus. Our detailed investigations will include genetic studies of swine influenza, immunological and virological studies of infection of pigs with the 'normal' swine and pandemic strains of the virus. We will study the level of transmission of the virus from pig to pig and investigate the clinical impact of the disease. This project will substantially add to the amount of data available on swine influenza so that we can properly estimate how much future risk is posed by this infection. Through comparing data from the pig studies and that derived from human cases occurring as the pandemic virus spreads we will be able to evaluate the pig as an animal model for suitability to studying pandemic influenza consequences for humans. The data generated from this grant will be used to study the rates of viral mutation and identify the specific mutations in influenza viruses that are associated with spread between pigs and people working with pigs. This will enable us to better predict the immediate threats from the pandemic virus mutating to become more virulent in people and pigs, particularly if the human pandemic virus becomes endemic in the pig population.