Combating Swine Influenza Initiative (model project)

30多年来首次人类流感大流行仍在继续，致病病毒是由两种不同的猪流感病毒组合而成的，一种起源于美国，另一种起源于欧洲。分析表明，这两种前体病毒在没有被检测到的情况下传播了大约9年，可能是在猪身上。流感病毒既能相互结合产生新病毒，又能迅速变异，这是它们在包括人类在内的新型哺乳动物中传播能力的重要特征。与大多数其他动物相比，猪对流感病毒的易感性更大，这使得它们作为可能发生这种病毒混合的动物具有重要意义。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一次。VLA的实验研究表明，猪可以感染大流行的人类病毒，更重要的是，可以将病毒传播给与它们共居的其他猪。由人类大流行病毒引起的猪流感疫情已在至少三个国家发生，很可能是在将病毒传播给猪的养猪户感染之后。在英国，一些猪是在非常密集的大种群中饲养的，如果这些农场感染了大流行流感病毒，将产生大量病毒，给照顾猪的农民带来不可预测的后果。人类大流行病毒源于猪流感病毒，猪对大流行病毒的易感性，以及世界各地养猪场的感染，在它们潜在的“混合容器”角色的背景下，对人类和猪的健康提出了几个迫在眉睫的重要问题和挑战。这笔赠款与平行的人口赠款申请一起，旨在回答其中一些问题，并通过这样做，提供直接的科学证据基础，为旨在将大流行对人类和动物的影响降至最低的政策提供参考。我们将考虑到猪的个体临床表现，包括导致疾病征兆的宿主或‘病人’机制，以及病毒的传播，来确定大流行病毒向猪传播的后果。这些研究将考虑到，一些猪可能通过先前的“正常”猪流感感染而自然部分免疫。我们将利用这项工作来估计猪感染大流行病毒可能对公共卫生构成的挑战。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。我们将研究该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现有数据量，以便我们能够正确估计这种感染构成的未来风险有多大。通过将猪研究的数据与大流行病毒传播时人类病例的数据进行比较，我们将能够评估猪作为动物模型是否适合研究大流行流感对人类的后果。这笔赠款产生的数据将用于研究病毒变异率，并识别与猪和与猪打交道的人之间的传播有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病毒变异对人和猪的直接威胁，特别是如果人类大流行病毒在猪群中成为地方病的话。

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.