牛病毒性腹泻病毒致病机制研究进展

牛病毒性腹泻（bovine viral diarrhea，BVD）和黏膜病（mucosal disease，MD）均是由牛病毒性腹泻病毒（bovine viral diarrhea virus，BVDV）感染引发的传染病，严重威胁世界养牛业的发展。文章概述了BVDV分型及其分子生物学特征，并从急性感染、经胎盘或子宫感染、持续性感染和黏膜病4个方面总结了近期国内外BVDV致病机制的研究进展。根据序列保守性及是否致细胞病变可将BVDV分为两种基因型和两种生物型，其中，新发现的"HoBi"株归类为瘟病毒属。BVDV基因进化很快，基因组编码4种结构蛋白和8种非结构蛋白，编码蛋白在病毒的复制、翻译及在宿主致病过程中发挥重要作用。BVDV致病机制复杂，急性感染会造成病毒血症、繁殖障碍、免疫抑制等，急性感染牛发生腹泻的原因与BVDV感染胃肠道的肌层、黏膜下层并干扰肠道神经的正常功能相关，非致细胞病变型（NCP）BVDV是造成急性感染的病因。胚胎感染BVDV取决于病毒首次侵袭时胎儿在子宫内的生长阶段。NCP型BVDV具有抑制胎儿体内产生Ⅰ型干扰素的能力，致使该病毒在宿主中得以生存并形成持续性感染牛，当持续性感染牛再次感染与NCP型BVDV高度同源的致细胞病变型（CP）毒株时直接诱发黏膜病。两种生物型的产生是发生持续性感染和黏膜病的重要因素，NCP型可向CP型BVDV进行转化。本综述有助于发现控制BVD-MD传播的新途径，为消灭该病和新型疫苗的研制提供参考。

Research Progress on Pathogenesis of Bovine Viral Diarrhoea Virus

Bovine viral diarrhea (BVD) and mucosal disease (MD) are all infectious diseases caused by the infection of bovine viral diarrhea virus (BVDV).The diseases threaten the development of the cattle industry seriously.This article briefly summarized the genotyping and molecular biological features of BVDV.BVDV can be divided into two genotypes and two biotypes according to sequence conservation and cytopathic effect.The newly discovered ‘HoBi’ strain is classified as Pestivirus genus,and the BVDV gene has evolved rapidly.The genome encodes four structural proteins and eight non-structural proteins.Coding proteins play an important role in the virus replication,translation and the host pathogenic process.The pathogenesis of BVDV is complicated.In this review,we summed up BVDV current researches on pathogenesis,including acute infection,uterine or placenta infection,persistent infection and mucosal disease,which was useful for discovery of new methods of control propagation.Acute infections can cause viremia,reproductive disorders,immunosuppression,and so on.The causes of diarrhea in acutely infected cattle are associated with the infection of the gastrointestinal muscularis,submucosa and normal function of the intestinal nerves by BVDV,and non-cytopathic (NCP) BVDV is the cause of acute infection.The mechanism of BVDV infection in embryos is more complicated,which depends on the fetal growth stage in the uterus during the first invasion of BVDV.NCP BVDV has the ability to inhibit the production of type Ⅰ interferon in the fetus causing the virus to survive in the host and forming a persistent infected cow.Mucosal disease is directly induced when the persistently infected cow re-infects a cytopathic (CP) strain that is highly homologous to NCP BVDV.Both biotypes are important factors in the development of persistent infection and mucosal disease.NCP BVDV can be transformed into CP BVDV.These fundamental researches are important for eliminating of BVD-MD and providing a basis for the development of new vaccines.