朊病毒是一种无核酸、非常规病毒，可引起人类和其他动物中枢神经系统慢性致死性感染。本项目拟围绕朊病毒持续感染和致病机理的四大科学问题，结合现代组学（蛋白质组、蛋白修饰谱、转录谱等）结果，采用分子/细胞生物学、新型电镜形态学、实验动物学（感染性实验、转基因动物）和临床流行病学相结合的技术手段，从群体、个体组织、细胞和分子层面，从朊病毒侵入、静止潜伏、形态发生、快速增殖、宿主免疫、病理损伤、疾病发生时间节点，从病原和宿主两个方面多维度，系统开展（1）朊病毒持续感染复制和转化过程中的形态学变化的研究（2）脑组织微环境生物活性因子变化对朊病毒增殖和纤维化影响的研究；（3）宿主天然免疫在朊病毒清除和神经损伤中作用的研究；（4）朊病毒跨种属感染体外和体内研究。进而从不同层面更加全面的阐明朊病毒形成和持续感染过程中与宿主防御体系的相互作用。

Prion is an inconvenient pathogen without nucleotide causing chronic and fatal infection in the central nerve systems of humans and other species. Four pivotal scientific problems in the fields of prion persistent infection and the pathogenesis of prion disease are planned to be systematically analyzed from the time-points of prion penetration, latent, morphology and development, rapid proliferation, host immunoresponse, neuropathological abnormality and disease onset, from the levels of molecule, cell, tissue and population, and from the sides of pathogen and host, using combined the results of proteomics, protein modification spectrum and transcript profile as well as methodologies of modern techniques of electron microscope morphology, molecular and cellular biology with the classical tools of animal experimental science (infectious test and transgenic mouse) and clinical epidemiology. Four major research components are designed, including (1) morphologic changes in the process of prion persistent infection, replication and conversion, (2) the synthetical influences of the changes of functional agents in brain microenvironment on prion replication and fibrillization, (3) the role of host innate immune in prions clearance and nerve damage, (4) the interspecies infections of prions in vitro and in vivo. Through those systematical studies from various points of views, the interaction between pathogen and host in brain tissue during prion formation and persistent infection is expected to be precisely clarified.