马立克氏病病毒调控Ⅰ型干扰素信号通路的研究进展

马立克氏病(Marek's disease,MD)是由马立克氏病病毒(Marek's disease virus,MDV)引起的鸡的淋巴细胞增生性肿瘤疾病,主要以侵染外周神经系统和内脏器官为主。先天性免疫是机体抵御病毒的第一道防线,病毒入侵后机体会迅速募集免疫细胞同时诱导产生干扰素(Interferon,IFN)和其他细胞因子抑制病毒的复制,其中Ⅰ型IFN在先天性免疫中发挥重要的抗病毒免疫作用。MDV在不断的进化过程中产生了多种免疫逃避机制,过去十年的研究发现越来越多的MDV蛋白参与调控Ⅰ型IFN信号通路。文章从Ⅰ型IFN产生的级联反应机制、MDV及与之亲缘关系相近的疱疹病毒蛋白调控Ⅰ型IFN表达的信号通路等方面进行综述,旨在帮助研究人员更好地理解MDV逃避宿主抗病毒天然免疫应答的分子机制,为更深入的研究开拓新思路。     

猪流行性腹泻病毒逃避宿主干扰素抗病毒作用机制的研究进展

猪流行性腹泻病毒（porcine epidemic diarrhea virus,PEDV）是一种全球分布的α冠状病毒,能引起仔猪流行性腹泻,猪流行性腹泻一旦暴发会给养殖业带来巨大的经济损失。在病毒感染期间,Ⅰ型干扰素（type Ⅰ interferon,IFN-Ⅰ）是先天性抗病毒反应的关键介质。大多数冠状病毒通过限制IFN的产生和IFN应答的激活而产生一些策略以规避IFN应答。然而,PEDV颉颃IFN抗病毒作用的分子机制尚未完全清楚。猪感染PEDV后,机体的先天免疫不能有效抵抗PEDV的侵害,PEDV通过限制或阻断IFN的功能和隐藏自身的病原体相关分子模式（pathogen-associated molecular patterns,PAMP）两种途径逃逸宿主先天免疫。在此过程中,PEDV的结构蛋白和非结构蛋白及一些蛋白酶起到了关键作用,核衣壳（nucleocapsid,N）蛋白能抑制IFN-Ⅰ的产生,协助病毒逃避机体的抗病毒天然免疫,木瓜样蛋白酶通过去泛素化酶活性阻断天然免疫信号通路,PEDV也可通过阻断双链核糖核酸（double-stranded RNA,dsRNA）诱导IFN-Ⅰ的产生,以逃避宿主的先天免疫。这些研究为深入了解IFN在PEDV致病过程中的作用及PEDV逃避IFN抗病毒的机制提供了理论依据,并有助于深入了解病毒与宿主先天性免疫之间的关系,同时也为PEDV的防治及PEDV疫苗的研发提供参考。     

猪流行性腹泻病毒逃避宿主干扰素抗病毒作用机制的研究进展

猪流行性腹泻病毒(porcine epidemic diarrhea virus,PEDV)是一种全球分布的α冠状病毒,能引起仔猪流行性腹泻,猪流行性腹泻一旦暴发会给养殖业带来巨大的经济损失。在病毒感染期间,Ⅰ型干扰素(typeⅠinterferon,IFN-Ⅰ)是先天性抗病毒反应的关键介质。大多数冠状病毒通过限制IFN的产生和IFN应答的激活而产生一些策略以规避IFN应答。然而,PEDV颉颃IFN抗病毒作用的分子机制尚未完全清楚。猪感染PEDV后,机体的先天免疫不能有效抵抗PEDV的侵害,PEDV通过限制或阻断IFN的功能和隐藏自身的病原体相关分子模式(pathogen-associated molecular patterns,PAMP)两种途径逃逸宿主先天免疫。在此过程中,PEDV的结构蛋白和非结构蛋白及一些蛋白酶起到了关键作用,核衣壳(nucleocapsid,N)蛋白能抑制IFN-Ⅰ的产生,协助病毒逃避机体的抗病毒天然免疫,木瓜样蛋白酶通过去泛素化酶活性阻断天然免疫信号通路,PEDV也可通过阻断双链核糖核酸(double-stranded RNA,dsRNA)诱导IFN-Ⅰ的产生,以逃避宿主的先天免疫。这些研究为深入了解IFN在PEDV致病过程中的作用及PEDV逃避IFN抗病毒的机制提供了理论依据,并有助于深入了解病毒与宿主先天性免疫之间的关系,同时也为PEDV的防治及PEDV疫苗的研发提供参考。     

禽干扰素抗病毒机制及在家禽生产中的应用

干扰素(IFN)是一类由活化的T细胞和自然杀伤细胞产生的具有广谱抗病毒活性和免疫调节功能的糖蛋白。当病毒入侵机体时,干扰素最先发挥作用。干扰素在抵抗病毒感染和干扰病毒复制等方面起重要作用,被广泛应用于家禽流行性病毒等疾病的预防和治疗中。文章就几种不同类型禽干扰素的抗病毒机制进行综述,包括禽干扰素的产生及分类、作用机制、应用等,为其在家禽生产中的应用提供参考。     

干扰素作用机制及其在抗口蹄疫病毒中的应用研究进展

干扰素(interferon,IFN)是人和动物细胞受到适宜刺激产生的一种微量的、具有高度生物学活性的糖蛋白,是一种具有广谱抗病毒、抗肿瘤、抗多发性硬化、抑制细胞增长和免疫调节作用的细胞因子。自20世纪50年代末发现干扰素以来,相关研究取得了巨大进展。文章综述了干扰素的抗病毒机制及其在抗口蹄疫病毒中的应用进展。     

新城疫病毒P基因的RNA编辑及其抗干扰素作用

新城疫病毒的P基因转录过程中在第484特定位置插入非模板G碱基发生RNA编辑现象 ,产生两种非结构蛋白 ,即V和W蛋白。文章综述了副黏病毒 (主要是新城疫病毒 )P基因RNA编辑的机理、产生的非结构蛋白与机体内干扰素之间的相互作用及相关研究进展     

禽干扰素基因工程表达技术研究进展

干扰素是一组具有多种功能的活性蛋白(主要是糖蛋白),是一种由单核细胞和淋巴细胞产生的细胞因子。根据干扰素产生的来源和结构不同可分为α干扰素、β干扰素和γ干扰素三类。研究发现干扰素通过细胞表面受体作用使细胞产生抗病毒蛋白,从而抑制病毒的复制,同时它还可增强自然杀伤细胞(NK细胞)、巨噬细胞和T淋巴细胞的活力,从而起到免疫调节作用,并增强抗病毒能力。由于干扰素几乎能抵抗所有病毒引起的感染,加     

Viperin在抗病毒免疫中的作用研究进展

病毒感染激活宿主细胞先天性免疫信号通路级联反应,通过产生干扰素、抗病毒蛋白等来限制病毒复制和防止感染。Viperin是一种在物种间相对保守、参与先天性免疫的内质网相关抗病毒蛋白,通过与病毒蛋白、某些细胞内蛋白的相互作用调节信号转导过程,发挥抑制多种病毒增殖的广谱抗病毒作用。目前,对Viperin蛋白发挥抗病毒和免疫调节作用的功能域、作为自由基SAM酶家族成员发挥作用的机制有了新的认识,但对Viperin能够在不同病毒感染细胞内发挥广泛作用的确切机制仍不是很清楚。论文就Viperin的基本生物学特性、发挥不同抗病毒机制的研究进展进行综述。     

Mx抗病毒蛋白在水禽业抗病育种中的研究展望

Mx蛋白是I型干扰素（IFN）诱导下产生的具有抗病毒功能的蛋白质,属于大分子GTP酶动态蛋白（dynamin）超家族,大多数的脊椎动物有1～3个不同细胞内定位的Mx蛋白异构体,一般定位于核内或胞质中。Mx蛋白对RNA和DNA病毒具有广谱的抗病毒能力;其特征在N端有一个三联体GTP结构域和发动蛋白家族的结构特征序列,以及C端高度保守的亮氨酸拉链结构域,该区域是进行亚细胞定位及与病毒直接作用的区域。本文介绍了Mx蛋白发现、结构、抗病毒活性机制,并对水禽类MX蛋白在水禽抗病育种中的应用进行了展望。     

哈兽研在宿主天然免疫系统抗流感病毒作用机制研究取得进展

正近日,中国农业科学院哈尔滨兽医研究所国家禽流感参考实验室在TRIM家族蛋白抗流感病毒天然免疫机制研究方面取得重要进展,该研究发现TRIM35是维甲酸诱导基因I(RIG-I)信号通路介导Ⅰ型干扰素(IFN)产生的正调控分子,阐明了TRIM35抑制流感病毒复制和致病的分子机制。TRIM家族蛋白具有的抗病毒作用和天然免疫调节功能是近年来天然免疫领域的研究热点。该研究得到了国家重点研     

Paramyxovirus and reovirus infections in wild-caught Mexican lizards (Xenosaurus and Abronia spp.).

Virus isolation attempts were carried out on wild-caught Xenosaurus grandis, X. platyceps, and Abronia graminea from Mexico. These animals were also tested for exposure to paramyxoviruses and reoviruses. Pharyngeal and cloacal swabs were collected from 30 lizards, and blood was collected from 23 lizards. A cytopathogenic virus was isolated from the cloacal swab of one of the X. platyceps. The isolate was identified as a paramyxovirus on the basis of its sensitivity to chloroform, resistance to 5-iodo-2'-deoxyuridine, size and morphology of the viral particles, hemagglutination of chicken erythrocytes, and serologic reaction with paramyxovirus-specific antisera. Antibodies against the paramyxovirus isolated in this study were found in four animals from three species. Antibodies against a different paramyxovirus isolated from a monitor lizard were found in seven animals from three species, showing that all the species tested are susceptible to paramyxovirus infections. Antibodies to a reptilian reovirus were found in three of the X. grandis.     

Effect of Propionibacterium acnes-containing immunostimulant on interferon-gamma (IFNγ) production in the neonatal foal

Production of the Th1 cytokine interferon gamma (IFNγ) is associated with resistance to intracellular pathogens, including Rhodococcus equi. While neonatal foals are initially deficient in IFNγ production, expression of this cytokine increases throughout their first year of life. This is presumably the result of stimulation by environmental antigens including pathogen associated molecular patterns (PAMPS) signaling through toll-like receptors (TLR). This increased expression of IFNγ is likewise associated with an age-related resistance to R. equi infection. While immunostimulants containing PAMPS have been administered to adult horses in an attempt to modify their immune response, the effect of these materials on IFNγ expression in foals is unknown. The main objective of this study was to determine the effect of administering a commercial immunomostimulant EqStim? (Propionibacterium acnes) on IFNγ production measured using intracellular staining (IFNγ) and RT-PCR.     

两株H1N1亚型猪流感病毒NS1蛋白抑制Ⅰ型IFN功能比较

本研究分离得到两株猪源H1N1流感病毒,通过进化树分析发现分别是欧亚类禽H1N1猪流感病毒和类鸭源H1N1猪流感病毒,为了研究两株毒株的NS1蛋白对Ⅰ型IFN产生的抑制能力,分别构建了2个毒株的NS1基因的真核表达载体,将NS1真核表达质粒、Ⅰ型IFN报告质粒与干扰素刺激质粒RIG-I共转染293T细胞,利用双荧光素酶...     

The molecular biology of the porcine paramyxovirus LPMV.

Protein and genomic studies of a previously uncharacterized porcine paramyxovirus (designated LPMV) confirmed that it was a member of the paramyxovirus genus. The nucleotide sequences and deduced amino acids of the complete P-gene, M-gene, F-gene and HN-gene as well as the intergenic sequences have been determined. Comparative sequence analysis of the M-gene of LPMV revealed the closest relationship of LPMV was to human mumps virus with a homology of 46% and 55% at the amino acid and nucleotide levels respectively. The P-gene of LPMV is transcribed to V protein mRNA and by editing of the gene to the P protein mRNA. The LPMV P-gene has the coding capacity for an additional protein of 126 amino acids, a C protein.     

鸭Ⅰ型禽副粘病毒YH99V株HN基因的克隆和序列分析

在浙江地区进行鸭病病因的调查过程中，从患病鸭群中分离到一株引起鸭产蛋锐减而不死亡的病毒，经鉴定该病毒属于禽副粘病毒Ⅰ型，命名为YH99V株。以YH99V株的基因组RNA为模板，通过RT—PCR一步法扩增出其HN基因的cDNA片段，然后将其克隆至pMD18-T载体中，对其进行序列测定。测序后拼接出HN基因的序列长度为1785bp，该基因的ORF总长为1734bp，编码577个氨基酸。将YH99V株HN基因序列和推导的氨基酸序列与新城疫毒株的HN基因相应序列比较后发现，它们的核苷酸序列同源性分别在82．1％～99．7％，氨基酸序列同源性为87．2％～99．5％。在同源性比较的基础上，进一步绘制了Ⅰ型禽副粘病毒株HN基因的系统发育树。这对于Ⅰ型禽副粘病毒毒力基因的功能分析和该病的分子流行病调查有着重要的意义。     

Recombinant DNA technology for the preparation of subunit vaccines

Recombinant DNA technology appears to be on the verge of producing safe and effective protein vaccines for animal and human diseases. The procedure is applicable to most viruses because their isolated surface proteins generally possess immunogenic activity. Strategies used for the preparation and cloning of the appropriate genes depend on the characteristics of the viral genomes: whether DNA or RNA; their size, strandedness, and segmentation; and whether messenger RNA are monocistronic or polycistronic. Cloned surface proteins of foot-and-mouth disease and hepatitis B viruses are being tested for possible use as practical vaccines. Two doses of the cloned foot-and-mouth disease viral protein have elicited large amounts of neutralizing antibody and have protected cattle and swine against challenge exposure with the virus. Surface proteins have also been cloned for the viruses of fowl plague, influenza, vesicular stomatitis, rabies, and herpes simplex. Cloning is in progress for surface proteins of viruses causing canine parvovirus gastroenteritis, human papillomas, infectious bovine rhinotracheitis, Rift Valley fever, and paramyxovirus diseases. In addition, advances in recombinant DNA and other facilitating technologies have rekindled interest in the chemical synthesis of polypeptide vaccines for viral diseases. The bioengineering of bacterial vaccines is also under way. Proteinaceous pili of enterotoxigenic Escherichia coli are being produced in E coli K-12 strains for use as vaccines against neonatal diarrheal diseases of livestock.     

小鹅瘟－鹅副黏病毒病二联油乳剂灭活疫苗的研究

为了有效防制小鹅瘟和鹅副黏病毒病对雏鹅的危害,分别选用免疫原性良好的小鹅瘟JLDA株和鹅副黏病毒JLSY株制作抗原液,应用PALL浓缩技术进行浓缩,保证灭活病毒抗原含量足,比例均衡。选取10号白油佐剂,按油相与水相比1∶1配制成复相制备二联灭活苗,黏稠度低。结果显示,对鹅的免疫效力不低于相应单苗,两种病毒之间没有交互抑制作用,且二联灭活苗安全性能好,疫苗吸收良好。种、雏鹅产生抗体快,免疫种、雏鹅,具有产生免疫力早,保护期长等特点,于2~8 ℃至少保存12个月。     

新城疫疫苗预防鸭副粘病毒病效果

为探讨新城疫疫苗对鸭副粘病毒病的预防效果,应用鸡新城疫活疫苗(I系和Lasota株)免疫2日龄雏番鸭,分别于免疫后7 d攻毒,并采血测定HI抗体。结果显示鸡新城疫I系活疫苗和Lasota疫苗对番鸭均安全,单独或混合应用均能有效抵抗鸭副粘病毒和新城疫标准毒(F48E8)的攻击;同时番鸭免疫后7 d I系疫苗诱导的HI抗体水平显明高于Lasota疫苗,而攻毒后35 d的HI抗体水平则以Lasota疫苗组高于I系疫苗组。上述结果表明新城疫I系和Lasota疫苗均可用于预防鸭副粘病毒病。     

禽副粘病毒Ⅰ型（APMV-1）分子生物学研究进展

主要介绍了禽副粘病毒1型两种主要的囊膜糖蛋白基因的特点，结合最近出现的几种分类方法，描述了两种新近出现的副粘病毒病，强调了禽副粘病毒所表现出的新的致病特点，为研究禽副粘病毒病的防制方法提供了理论依据。     

IFN gamma and IL-4 production by CD4, CD8 and WC1 gamma delta TCR(+) T cells from cattle lymph nodes and blood

The synthesis of IFN gamma and IL-4 by CD4, CD8 and WC1 gamma delta TCR(+) T cell sub-populations, and T cells stained with activation/memory-sub-set markers has been examined by flow cytometric analysis. Cells from blood, prescapular, bronchial and mesenteric lymph nodes and Peyer's patches were incubated with phorbol 12-myristate 13-acetate (PMA), ionomycin and brefeldin-A before staining. Lymphocytes that stained for cytoplasmic IFN gamma were evident within the CD4 and CD8 populations from all tissues and also in the WC1 population from lymph nodes. IL-4 producing cells were primarily evident within the CD4 population. IFN gamma synthesis was evident within both CD45RO(+) and CD45RB(+) populations, but IL-4 synthesis was predominantly by cells that were CD45RO(+)/CD45RB(-). Expression of CD62L is not related to functional memory in CD4(+) T cells from cattle and CD62L(+) cells, particularly from the lymph nodes draining the skin and the lungs, stained with mAb to IFN gamma and IL-4. The findings indicate that at least for CD4(+) T cells, where CD45 isoform expression is related to functional memory, these two cytokines are produced predominantly by cells with a memory phenotype. The observation that some WC1(+) cells produce IFN gamma implies the presence of distinct sub-sets of this gamma delta TCR(+) population cattle and suggests a functional role.