冠状病毒受体的研究进展

近年来多种感染人或家畜的冠状病毒病轮番出现,给人类社会的经济和公共卫生安全带来很大危害。特别是在2019年底出现并在全球迅速蔓延的SARS-CoV-2,由此引发的新型冠状病毒肺炎(COVID-19)在2019年12月至2020年3月之间在全球范围内造成超过7万人死亡。冠状病毒感染宿主的第一步是识别宿主细胞膜受体分子并与之结合,随后启动入侵使病毒基因组进入宿主细胞内部。因此冠状病毒细胞受体的阐明对于了解病毒的宿主与组织嗜性具有重要意义,同时也有助于了解病毒的致病与传播机制以及新型抗病毒药物研发。本文介绍了近年来主要的冠状病毒受体的最新研究进展,包括血管紧张素2(the angiotensin converting enzyme 2,ACE2)、氨基肽酶N(aminopeptidase N,APN)、二肽酰肽酶4(dipeptyl peptidase 4,DPP4)、唾液酸(sialic acid,SA)和癌胚抗原相关细胞黏附分子1(carcinoembryonic antigen-related cell adhesion molecule 1,CEACAM1)等。     

禽流感病毒宿主特异性与致病性的分子基础研究进展

禽流感病毒不断重排和变异导致新型流感病毒不断出现,其中有些毒株已经获得了感染哺乳动物的能力,严重危害人类公共卫生安全。近年来,对于禽流感病毒致宿主特异性和致病性的研究取得了一定进展。病毒蛋白某些氨基酸位点的突变就能够改变病毒的宿主特异性,使病毒能够跨宿主传播。而且,病毒的RNA聚合酶、NS1非结构蛋白和几种新发现的病毒蛋白都与病毒的致病性密切相关。论文阐述了禽流感病毒宿主特异性与致病性的分子基础,为禽流感跨物种传播机制研究及防控工作提供参考。     

鸡传染性支气管炎病毒受体研究进展

鸡传染性支气管炎是一种世界性分布的严重影响养鸡业的高度接触性传染病,其病原是一种最早发现的冠状病毒鸡传染性支气管炎病毒(IBV)。IBV入侵细胞的受体是目前IBV研究中的热点之一。已知IBV囊膜上的纤突蛋白(S)是宿主组织和细胞嗜性及致病性的主要决定因素,S蛋白通常断裂为S1和S2两部分,S1与宿主细胞膜上的细胞受体相结合,在S2的作用下病毒囊膜与宿主细胞膜融合,IBV与受体结合之后于中性或微碱性pH时发生构象改变,从而获得病毒进入宿主细胞的能力。对于IBV的受体研究主要集中于IBV可能使用的几种功能性受体,包括氨肽酶N、唾液酸、硫酸乙酰肝素等。     

科技

正哈尔滨兽医所在狂犬病病毒感染机制研究方面取得重要进展近日,中国农业科学院哈尔滨兽医研究所重要人兽共患病与烈性外来病研究团队,在狂犬病病毒(RABV)致病机制研究方面取得重要进展,发现代谢型谷氨酸受体2(mG luR 2)为RABV入侵神经细胞的全新受体,研究系首次报道重要神经信号传导分子——代谢型谷氨酸受体家族成员与嗜神经性病毒存在直接相互作用关系。相关研究在《公共科学图书馆一病原体(PLOS Pathogens)》上在线发表。     

病毒受体研究进展

病毒通过与宿主易感细胞表面的特异性受体结合而启动其复制过程。宿主的组织及细胞表面特定受体是决定病毒入侵途径、扩散方式及决定宿主发病特点的主要因素：因此，开展对病毒受体的研究具有重要意义。从受体角度阐明病毒入侵机制，是预防和治疗病毒性疾病的药物及疫苗研发重要领域。     

MicroRNA研究概述

MicroRNA(miRNA)是一类真核生物内源性非编码的单链小分子RNA,长约21nt~23nt。越来越多的miRNA在动物细胞和植物组织中发现,这些成熟的小分子RNA是从具有发夹结构的前体miRNA(pre-miRNA)剪切出来,通过与靶mRNA分子互补结合而抑制蛋白翻译或导致mRNA降解,从而调控靶基因的表达。miRNA是一类重要的基因调控子,在机体的基因表达调控、细胞分化和凋亡以及抗病毒防御中发挥重要的作用。深入理解miRNA介导的宿主与病毒之间的相互调节作用,对于阐明病毒的致病机理与制定治疗策略具有深远的意义。     

机体识别病毒核酸的几种分子模式及途径

近些年机体病原相关模式受体及其识别分子机制的研究,极大地促进了先天性分子免疫学的发展,并成为现代免疫学研究的重点和热点领域。作者通过机体识别病毒核酸的Toll样受体(Toll-like receptors,TLRs)、RIG-I样受体(RIG-I like receptors,RLRs)、NOD样受体(NOD-like receptors,NLRs)和DAI(DNA-dependent activatorof interferon-regulatory factors,DAI)等模式识别分子的细胞定位、分子结构及其识别病毒核酸途径的介绍,系统、全面地探讨了宿主机体如何全方位识别和消除入侵病毒的分子免疫防御途径,为抗病毒药物和疫苗的设计以及抗病育种提供了理论依据。     

副黏病毒糖蛋白的结构与功能研究进展

副黏病毒是一类包含多种能引起人和动物严重疾病的负链RNA病毒。其病毒颗粒囊膜上排列有两种糖蛋白，分别是识别并结合宿主受体的附着蛋白(hemagglutinin neuraminidase/hemagglutinin/glycoprotein, HN/H/G)和介导病毒颗粒囊膜与宿主细胞膜融合的融合蛋白(fusion protein, F)。这两种糖蛋白通过与病毒受体及细胞膜的互相作用介导了病毒与宿主细胞的特异性识别、结合及融合过程，最终使病毒基因组进入宿主细胞质开启复制过程。由于糖蛋白是主要的病毒抗原及中和抗体靶点，因此近年来对副黏病毒糖蛋白的研究在不断的深入探索。就副黏病毒糖蛋白在其结构、功能及其相互作用方面的研究进展进行了综述，以期为治疗性抗体和疫苗的合理开发提供理论基础。     

口蹄疫病毒整合素受体研究进展

口蹄疫病毒(Foot-and-Mouth Disease Virus,FMDV)感染宿主细胞首先是病毒与被感染细胞表面的病毒受体结合,通过网格蛋白介导的内吞途径,酸化的内吞泡运输进入细胞内,然后衣壳迅速解体,释放出基因组RNA,细胞受体决定口蹄疫病毒宿主特异性和组织特异性.对口蹄疫病毒细胞受体的研究将有助于揭示口蹄疫病毒的感染机制、复制过程、致病机理和疫病预防及治疗等,细胞受体的研究已经成为目前口蹄疫病毒研究中的重点领域之一,论文就近年来FMDV整合素受体研究现状进行了综述,并对其发展进行了展望.     

传染性支气管炎病毒受体研究进展

传染性支气管炎(IB)是由冠状病毒科传染性支气管炎病毒(IBV)引起的高度接触性传染病。该病在世界各地均有发生,给全球养禽业造成巨大的经济损失。IBV感染宿主细胞的第一步是病毒与细胞表面的受体结合,介导病毒颗粒进入细胞内。IBV病毒受体的研究对于揭示IBV的致病和免疫机理具有重要价值。文中就近年来发现的氨基肽酶N、硫酸乙酰肝素和唾液酸受体作综述。     

Caliciviruses: an overview.

Several caliciviruses are known to cause diseases in animal and man. Amongst them are vesicular exanthema virus of swine (VESV), feline calicivirus, rabbit hemorrhagic disease virus (RHDV), and Norwalk and Sapporo-like viruses; the latter viruses cause gastroenteritis in man. In this paper, an overview of caliciviruses is presented, with particular emphasis on the molecular aspects. The unique properties as compared to other related families of positive-stranded RNA viruses will be discussed. Many findings about the molecular biology of caliciviruses came from systems that are difficult to work with, such as RHDV, which can thus far only be propagated either in animals or in primary rabbit hepatocyte cultures. Therefore, the review will concentrate on RHDV.     

Molecular virology of feline calicivirus.

Caliciviridae are small, nonenveloped, positive-stranded RNA viruses. Much of our understanding of the molecular biology of the caliciviruses has come from the study of the naturally occurring animal caliciviruses. In particular, many studies have focused on the molecular virology of feline calicivirus (FCV), which reflects its importance as a natural pathogen of cats. FCVs demonstrate a remarkable capacity for high genetic, antigenic, and clinical diversity; "outbreak" vaccine resistant strains occur frequently. This article updates the reader on the current status of clinical behavior and pathogenesis of FCV.     

A simple and rapid method for isolation of caliciviruses from liver of infected rabbits

Rabbit Haemorrhagic Disease Virus (RHDV), a member of the Caliciviridae family, is the etiologic agent of Rabbit Haemorrhagic Disease (RHD); this viral disease is highly contagious and kills more than 90% of infected adult rabbits. Research on experimental calicivirus infection uses inocula obtained from livers of rabbits dying from calicivirus infection. This implies that caliciviruses have to be purified from liver homogenates. Current methods to isolate caliciviruses from rabbit livers are time consuming. We propose here a new procedure for fast purification of rabbit caliciviruses from liver homogenates that uses centrifugation through an iodixanol gradient. This method offers in approximately 2 h a sample with a high degree of calicivirus purity, as shown by its biochemical and immunocytochemistry analysis, which is also able to kill adult rabbits from RHD within 48 h of inoculation.     

Detection of St-Valerien-like viruses in swine, Italy

St-Valerien-like viruses are newly recognized porcine caliciviruses recently detected in Canadian swine farms. These viruses that appeared genetically closest to the Tulane non-human primate virus and noroviruses (NoVs), may represent members of a potential new genera within the Caliciviridae family. To date, there are no information on the epidemiology of these novel caliciviruses in other continents. In this study, 264 faecal samples collected from asymptomatic adult pigs were screened by RT-PCR using St-Valerien-like specific primers. Porcine caliciviruses, resembling St-Valerien-like viruses were identified in five animals. The 3' end of the genome of one of these strains, 25A/ITA, was determined, revealing close genetic relatedness to the newly discovered St-Valerien-like caliciviruses, identified in swine in Canada. The findings of this investigation demonstrate that St-Valerien-like viruses are not geographically restricted, since they were identified outside the North American continent where there were first signalled.     

Immunoelectron microscopic comparisons of caliciviruses

Using immunoelectron microscopy, 9 serotypes of vesicular exanthema of swine virus (VESV) were compared with 5 serotypes of San Miguel sea lion virus and 7 additional calicivirus isolates from marine animals. In addition, swine caliciviruses and marine caliciviruses were compared with the vaccinal strain of feline calicivirus (FCV) F-9. Of 9 VESV types, 8 showed common antigenicity with San Miguel sea lion virus. Of 9 VESV types, 2 showed common antigenicity with FCV F-9. All 12 marine caliciviruses showed common antigenicity with VESV, but not with FCV F-9.     

Feline calicivirus VP2 is involved in the self-assembly of the capsid protein into virus-like particles

Feline calicivirus (FCV) is considered the most common upper respiratory tract disease (URTD) associated pathogen in cats. We previously expressed FCV VP1 capsid protein in insect cells by baculovirus system and we observed that this protein self-assemble into virus-like particles (VLPs) different in size and lacking the typical cup-like depressions of caliciviruses. In the present study, VP1 and the small basic structural protein VP2 of FCV were individually expressed by baculovirus system. Coinfection of insect cells with both recombinant viruses resulted in VP1 and VP2 self-assembly to form depressions similar to native capsids in size and appearance, demonstrating that VP2 interacts with the VP1 protein in the formation of VLPs.     

Isolation rates of feline respiratory viruses in local cat populations

Respiratory and conjunctival secretions were collected from fifty-nine cats living in a rural environment and 128 cats living in an urban environment. All cats were showing some signs of respiratory disease. Feline caliciviruses or feline rhinotracheitis viruses were isolated from 16% and 56% of the cats from the urban and rural areas respectively. The caliciviruses were serologically related.     

Genetic analysis of a canine calicivirus: evidence for a new clade of animal caliciviruses.

This paper describes the relationship of a canine calicivirus, named No.48, to other human and animal caliciviruses, based on phylogeny of the 3' half of its genome. It was found that No.48 constitutes a unique lineage, most closely related but distinct from feline and San Miguel sea lion caliciviruses.     

Evidence for recombination in neboviruses

Neboviruses are bovine enteric caliciviruses (genus Nebovirus) associated with enteric diseases in calves. By screening the stools of calves collected from Italian herds using primers targeted to a conserved stretch in calicivirus RNA-dependent RNA-polymerase (RdRp), nebovirus RNA was detected in calves with enteritis (13.1%) but not in overtly health animals. Upon sequence analysis of the RdRp fragment, the Italian viruses formed a tightly conserved group and resembled closely the nebovirus prototype Nebraska/80/US. The sequence of a 2.2kb ORF1 fragment, spanning the 3' end of the RdRp and the full-length capsid coding region, of two nebovirus strains was determined, revealing marked genetic heterogeneity in the capsid protein, as the two Italian viruses were classified into two distinct capsid lineages, and suggesting a recombination event downstream the highly conserved shell (S) domain.