江西及周边省份猪流行性腹泻病毒分子流行病学和致病机理的研究

Porcine epidemic diarrhea (PED) is a highly contagious acute diarrheal disease caused by PED virus (PEDV), a member of the family Coronaviridae. Killed PEDV vaccines are being used for the prevention and control of PED. However, PED has been reemerging in immunized swine accompanied by an increased disease severity in recent years. A recent outbreak of PED swept more than10 provinces in southern China in 2010-2011, characterized by an almost 100% morbidity and 80%-100% mortality among neonatal piglets, resulting in more than one million piglets death. To reveal the mechanisms responsible for the severe form PED disease, we propose to investigate the molecular epidemiology of reemerging PEDVs currently circulating in Jiangxi and surrounding Provinces and the pathogenesis of predominant Chinese wild-type PEDV strains. We hypothesize that Chinese field strains of PEDV have altered in terms of pathogenecity, antigenecity, and immunogenecity, which leads to currently used PEDV vaccines fail to provide solid protection against the infections of those viruses. Viral Metagenomics, other state-of-the-art and conventional approaches in the fields of Molecular Virology, Epidemiology, Immunology, Biology and Bioinformatics will be employed to identify and characterize genetic and phenotypic variations at the entire genomic level of those reemerging virulent PEDVs; An in vitro comparison of the infection rate and replication ability of the viruses will be performed; Virus virulence, tissue tropism, replication property, and pathogenecity will be observed from the piglets naturally and experimentally infected with wild-type PEDVs. The achievement of the expected goal of this study will provide insights on molecular epidemiology of the wide-type PEDVs circulating in Jiangxi and surrounding provinces and elucidate the molecular basis of the viral pathogenesis, and thus benifit the development of next generation PEDV vaccines with improved efficacy and safety. Meanwhile it will also provide valuable knowledge for the development of novel diagnostic tools and shed lights for the discovery of the antivirals against PEDVs.

猪流行性腹泻（PED）是由PED病毒（PEDV）引起的一种高度传染性危害各年龄猪只的急性腹泻病，是重点防制的猪的传染病之一。近年来，PED在我国许多用灭活疫苗免疫接种的猪群中再度出现，并伴以高发病率（60%-100%）和仔猪的高死亡率（80%-100%）。导致此现象的原因，我们认为目前流行的PEDV野毒株在致病性、抗原性和免疫原性等方面发生了改变，使得现今使用的疫苗不能对PEDV野毒株感染提供有效免疫保护。为此，我们拟采用包括病毒宏基因组学技术在内的分子生物学技术和方法对江西和周边省份PEDV分子流行病学及发病机制进行研究:在全基因组水平上对疫苗株和流行野毒株进行分析比较，揭示它们的进化关系，确定它们的基因型和表型等重要分子生物学特征的异同；观察自然和人工感染猪的病理解剖及病理生理变化。为研发更有效和更安全的下一代PEDV疫苗、新的诊断工具和抗PEDV药物提供分子生物学和病理学科学依据。

根据申报书拟定的各项研究内容，我们采用包括病毒宏基因组学技术在内的分子生物学技术和方法对江西和周边省份PEDV分子流行病学及发病机制进行研究，在全基因组水平上对疫苗株和流行野毒株PEDV进行了分析比较，揭示了它们的进化关系，确定了它们的基因型和表型等重要分子生物学特征的异同；观察自然和人工感染猪的病理解剖及病理生理变化；高质量、超额完成了申请书拟定的各项预期指标/目标，取得了一系列重要数据和成果，项目取得的成果为研发更有效和更安全的新一代PEDV疫苗、新的诊断工具和抗PEDV药物提供分子生物学和病理学科学依据。