病毒逃逸补体的机制

补体系统是宿主免疫防御外来病原体的第1道防线,包括对病毒的防御.补体系统可通过黏附在病原体表面利于宿主细胞吞噬、形成膜攻击复合体导致病原体溶解、释放过敏毒素引起炎症反应等多条途径清除外来病原体.然而,在与宿主一起进化的过程中,某些病毒已经建立了逃逸补体系统的策略,这些策略包括编码补体调控蛋白、从宿主获得膜调控蛋白以及利用宿主膜补体受体进入宿主细胞.本文就病毒逃逸补体系统作用的策略的研究进展作一综述.     

流感病毒先天免疫应答和先天免疫逃逸的机制

流感病毒引起人类和动物的呼吸道感染已是全世界严重的经济和公共卫生问题。在感染早期,流感病毒会导致机体的先天免疫信号被激活,起到防御、清除病毒以及辅助适应性免疫应答的作用。但在与宿主共进化的过程中,流感病毒形成了多种逃逸策略,主要是通过病毒自身蛋白质阻断宿主天然免疫通路,抑制干扰素和炎性因子的生成。基于现有的研究成果,本文针对流感病毒先天免疫应答和先天免疫逃逸的机制做一扼要综述,这有助于加强流感病毒抗原进化的监测、探索疫苗和抗病毒药物的合理靶标,为更好地预防和控制该病提供有效的策略。     

非洲猪瘟病毒拮抗宿主cGAS-STING信号通路的研究进展

非洲猪瘟病毒（African swine fever virus,ASFV）拥有多种逃逸宿主免疫应答的策略,造成病毒难以被宿主清除。cGAS-STING信号通路介导的天然免疫在抗ASFV感染中发挥了重要作用,然而病毒编码的多个蛋白靶向该通路中的不同分子以拮抗宿主的I型干扰素应答。利用基因编辑技术敲除这些病毒基因后,ASFV对宿主的致病性降低,成为基因缺失疫苗的研制潜在靶点。本文对目前已知参与调控宿主cGAS-STING信号通路的病毒蛋白进行总结,旨在阐明这些蛋白免疫逃逸cGAS-STING信号通路的分子机制,加深对ASFV免疫逃逸策略的理解,以期为ASFV致病机制研究与疫苗创制提供参考。     

模式识别受体介导的肿瘤免疫耐受参与肿瘤转移

肿瘤细胞与宿主相互作用经历免疫警戒、免疫平衡和免疫逃逸过程,称为肿瘤免疫编辑。具有免疫逃逸能力是肿瘤细胞的标志性改变,也是肿瘤生长失控、转移和治疗失效的重要原因。病原微生物所含病原相关模式分子和肿瘤组织释放的损伤相关模式分子与肿瘤细胞及周围组织细胞和免疫细胞表达的模式识别受体相互作用,引起抑制性免疫微环境是导致肿瘤免疫耐受的关键。以肿瘤免疫耐受为药靶,使用小分子化合物或具有免疫刺激活性的生物制剂如单克隆抗体,可逆转肿瘤抑制性免疫微环境,打破肿瘤免疫耐受,抑制肿瘤细胞的生长和侵袭能力,从而降低肿瘤细胞转移和肿瘤致死率。     

肠道病毒71型逃逸宿主固有免疫的分子机制

肠道病毒71型(enterovirus type 71,EV-A71)感染常引起婴幼儿手足口病(hand,foot,and mouth disease,HFMD),严重者可伴有中枢神经系统并发症。近年来,EV-A71引起的手足口病已成为我国以及亚太地区迫切需要解决的公共卫生问题。目前,EV-A71的致病机制并不清楚,但逃逸宿主免疫应答被认为是其重要的致病机理之一。现主要就EV-A71逃逸宿主固有免疫的分子机制做一综述,概述近年来有关EV-A71如何利用其自身编码的2A pro、3C pro等非结构蛋白,影响宿主对病毒核酸的识别、IFN诱发生成及IFN信号通路的激活,从而逃逸宿主固有免疫的主要进展情况,并对抗病毒感染免疫治疗策略作简略讨论。     

一个细菌的致命之旅——嗜肺军团菌分泌系统及效应蛋白的研究进展

嗜肺军团菌是引起军团菌肺炎以及庞蒂亚克热的革兰氏阴性胞内病原细菌,嗜肺军团菌侵染宿主的主要特点是可以通过其IVB型毒力分泌系统,向宿主细胞内分泌超过150种的底物效应蛋白。通过这些效应蛋白的作用,嗜肺军团菌能够调整宿主细胞的胞内运输途径,改变内外环境来伪装自己的吞噬泡,干扰宿主的细胞周期,抑制宿主细胞的凋亡,从而有效逃避宿主细胞的防御功能,创造出理想的胞内增殖环境。最后,效应蛋白还可以帮助军团菌从宿主细胞中逃逸。目前,嗜肺军团菌已经成为"病原菌-宿主相互作用"的重要研究模型,其毒力分泌系统及其底物效应蛋白的功能也成为细胞微生物学的研究热点。对嗜肺军团菌分泌系统及效应蛋白的研究不仅能够帮助阐明病原细菌的致病机理,还有助于推动对宿主免疫机制的更深层次的研究。文章主要针对嗜肺军团菌的毒力分泌系统,尤其是IVB型分泌系统的结构和功能,以及底物效应蛋白的研究进展进行了综述,向读者展示出一个小小的细菌所拥有的那令人惊叹的、如此狡猾的生存策略和它精致的杀伤武器。     

对于军团菌的免疫遏制:宿主能否另辟蹊径?

嗜肺军团菌可引起严重的非典型肺炎,其特殊的Dot/Icm IVB型分泌系统转运近330种效应蛋白(大多数作为蛋白酶发挥功能)至宿主细胞,通过修饰细胞调节因子、抑制细胞凋亡等一系列措施调控宿主免疫应答以逃逸宿主免疫系统的监测,完成自身的增殖与侵染.嗜肺军团菌诱发的病原相关分子模式(pathogen-associated ...     

非编码RNA在胞内病原菌免疫逃逸与致病中的作用

非编码RNA(non-coding RNAs,ncRNAs)在细胞增殖、发育、分化、代谢、信号转导以及免疫调控中发挥重要调节作用。越来越多的研究证明,ncRNA在胞内病原菌的致病性和免疫逃逸中发挥重要调控作用。一方面ncRNA是细菌代谢、群体感应和毒力因子表达的调控因子,与胞内病原菌的致病性密切相关;另一方面ncRNA在调节宿主抗胞内病原菌免疫应答中发挥重要作用,深入研究ncRNA如何调节宿主免疫应答将有助于胞内菌免疫逃逸机制的研究。就非编码RNA在胞内病原菌免疫逃逸和致病中的作用作一综述。     

布鲁氏菌逃避宿主免疫机制的研究进展

布鲁氏菌病是由布鲁氏菌引起的一种人畜共患性传染病,可以对畜牧业生产和人类健康造成严重的危害。布鲁氏菌是兼性胞内寄生菌,在长期与宿主免疫系统的相互作用中,进化出了多种逃避宿主免疫应答的机制。该文主要概述了布鲁氏菌胞内循环过程和逃避宿主先天性免疫应答和适应性免疫应答的机制,以及通过激活非典型自噬途径、抑制细胞凋亡、调控细胞焦亡等方式建立慢性感染的策略,以期为进一步深入研究布鲁氏菌病以及病原与宿主的相互作用提供参考。     

丙型肝炎病毒基因突变与免疫逃逸

免疫逃逸（Immune evasion）是指病原体逃避机体免疫监控的现象。在宿主和病毒的长期共同进化过程中,病毒形成了各种逃选机制以逃避宿主的免疫监控,其中病毒基因变异是最主要机制。丙型肝炎病毒（Hepatitis C virus,HCV）在感染个体中表现出极高的基因异质性,能有效地逃逸机体免疫识剐和破坏宿主免疫应答的能力,HCV还可侵袭免疫细胞来抑制机体的免疫功能,而建立HCV持续性感染。了解HCV病毒突变与免疫逃逸机制将会为预防和控制丙型肝炎提供依据。     

Antiviral effects of β-defensin derived from orange-spotted grouper (Epinephelus coioides)

Defensins are a group of small antimicrobial peptides playing an important role in innate host defense. In this study, a β-defensin cloned from liver of orange-spotted grouper, Epinephelus coioides, EcDefensin, showed a key role in inhibiting the infection and replication of two kinds of newly emerging marine fish viruses, an enveloped DNA virus of Singapore grouper iridovirus (SGIV), and a non-enveloped RNA virus of viral nervous necrosis virus (VNNV). The expression profiles of EcDefensin were significantly (P < 0.001) up-regulated after challenging with Lipopolysaccharide (LPS), SGIV and Polyriboinosinic Polyribocytidylic Acid (polyI:C) in vivo. Immunofluorescence staining observed its intracellular innate immune response to viral infection of SGIV and VNNV. EcDefensin was found to possess dual antiviral activity, inhibiting the infection and replication of SGIV and VNNV and inducting a type I interferon-related response in vitro. Synthetic peptide of EcDefensin (Ec-defensin) incubated with virus or cells before infection reduced the viral infectivity. Ec-defensin drastically decreased SGIV and VNNV titers, viral gene expression and structural protein accumulation. Grouper spleen cells over-expressing EcDefensin (GS/pcDNA-EcDefensin) support the inhibition of viral infection and the upregulation of the expression of host immune-related genes, such as antiviral protein Mx and pro-inflammatory cytokine IL-1β. EcDefensin activated type I IFN and Interferon-sensitive response element (ISRE) in vitro. Reporter genes of IFN-Luc and ISRE-Luc were significantly up-regulated in cells transfected with pcDNA-EcDefenisn after infection with SGIV and VNNV. These results suggest that EcDefensin is importantly involved in host immune responses to invasion of viral pathogens, and open the new avenues for design of antiviral agents in fisheries industry.     

Iridoviruses associated with epizootic haematopoietic necrosis (EHN) in aquaculture

Systemic infections of teleost fishes caused by iridoviruses have recently been recognized in Australia, Asia, Europe and the USA. These iridoviruses are different from those of the established genera Lymphocystivirus and Goldfish Virus 1-like Viruses of the family Iridoviridae. The agents exhibit similar physicochemical properties, are antigenically related and prove to be of high virulence to different teleost fishes in aquaculture. The first iridovirus, epizootic haematopoietic necrosis virus, responsible for an epizootic outbreak of haematopoietic necrosis in redfin perch, was reported in Australia. Some years later, similar iridovirus epizootics occurred in sheatfish and catfish in Europe. The Australian and the European isolates proved to be antigenically related and showed properties in common with frog virus 3, the type species of the genus Ranavirus of the Iridoviridae. Further iridovirus isolates from fish, amphibians and reptiles exhibited a close relationship with each other and with frog virus 3. It is important to note that the Australian amphibian iridovirus, Bohle iridovirus, was experimentally transmitted to teleost fish inducing high mortalities. The occurrence of similar viruses in different host species in the aquatic environment and their inter-species transmission emphasize the importance of health control in aquaculture.     

Systemic iridovirus from threespine stickleback Gasterosteus aculeatus represents a new megalocytivirus species (family Iridoviridae)

Megalocytiviruses have been associated with epizootics resulting in significant economic losses in public aquaria and food-fish and ornamental fish industries, as well as threatening wild fish stocks. The present report describes characteristics of the first megalocytivirus from a wild temperate North American fish, the threespine stickleback Gasterosteus aculeatus. Moribund and dead fish sampled after transfer to quarantine for an aquarium exhibit had amphophilic to basophilic intracytoplasmic inclusions (histopathology) and icosahedral virions (transmission electron microscopy) consistent with an iridovirus infection. Phylogenetic analyses of the major capsid, ATPase, and DNA polymerase genes confirmed the virus as the first known member of the genus Megalocytivirus (family Iridoviridae) from a gasterosteid fish. The unique biologic and genetic properties of this virus are sufficient to establish a new Megalocytivirus species to be formally known as the threespine stickleback iridovirus (TSIV). The threespine stickleback is widely distributed throughout the northern hemisphere in both freshwater and estuarine environments. The presence of megalocytiviruses with broad host specificity and detrimental economic and ecologic impacts among such a widely dispersed fish species indicates the need for sampling of other stickleback populations as well as other North American sympatric marine and freshwater ichthyofauna.     

Outbreaks and risks of infectious spleen and kidney necrosis virus disease in freshwater ornamental fishes

We examined the distribution of iridoviruses in 10 freshwater ornamental fish species hatched in Korea and imported from other Asian countries using both 1-step and 2-step polymerase chain reation (PCR). None of the 10 fish species analyzed were free of iridovirus as shown by 2-step PCR positive results, and 3 species yielded 1-step PCR positive results with associated mortality. Cloned PCR amplicons of the adenosine triphosphatase (ATPase) and major capsid protein (MCP) genes in genomic DNA of iridovirus showed the same nucleotide sequences as that of infectious spleen and kidney necrosis virus (ISKNV) isolated from the mandarinfish Siniperca chuatsi. These results indicate the presence of ISKNV disease in various ornamental fish as new host species and that the disease is widespread throughout different Asian countries including Korea, Singapore and China. Such infections were either clinical with associated mortality (and 1-step PCR positive) or asymptomatic in fish that were externally healthy (and only positive in 2-step PCR). Molecular analyses of the K2 region performed on iridovirus samples isolated from freshwater ornamental fishes revealed deletion/insertion of repetitive sequences of various lengths (42 to 339 bp), depending on the ISKNV isolates, without substitutions. Experimental infection of pearl gourami Trichogaster leeri and silver gourami T. microlepis with a tissue homogenate of pearl gourami infected by ISKNV induced 70 and 20% cumulative mortalities in the pearl and silver gourami, respectively.     

Baculovirus genes affecting host function

Baculoviruses are insect-specific viruses. These large DNA viruses encode many genes in addition to those required to replicate and build new virions. These auxiliary genes provide selective advantages to the virus for invading and infecting host insects. Eight of these genes, which help the virus overcome insect defenses against invasion, are discussed. These include genes whose products help the virus traverse physical or physiological barriers and those that overcome host immune defenses.     

Cross-regulation between herpesviruses and the TNF superfamily members

Herpesviruses have evolved numerous strategies to subvert host immune responses so they can coexist with their host species. These viruses 'co-opt' host genes for entry into host cells and then express immunomodulatory genes, including mimics of members of the tumour-necrosis factor (TNF) superfamily, that initiate and alter host-cell signalling pathways. TNF superfamily members have crucial roles in controlling herpesvirus infection by mediating the direct killing of infected cells and by enhancing immune responses. Despite these strong immune responses, herpesviruses persist in a latent form, which suggests a dynamic relationship between the host immune system and the virus that results in a balance between host survival and viral control.     

口蹄疫病毒与宿主细胞的相互作用研究进展

口蹄疫病毒（FMDV）导致了偶蹄动物口蹄疫的发生,它是一类有着自身特点的RNA病毒。首先,FMDV衣壳蛋白VP1识别结合宿主细胞膜上的整联蛋白等受体,以内吞的方式进入细胞,利用宿主细胞成分完成病毒蛋白的合成。这些新合成的L^pro、2C和3C^pro等病毒致病因子进一步抑制宿主基因的转录和翻译,诱导细胞凋亡和白噬,并抑制干扰素介导的一系列先天性和获得性免疫反应。宿主则在病毒侵染细胞的初期,利用病毒识别受体等来识别病毒并诱导合成干扰素等细胞因子,介导多种免疫反应以清除病毒。病毒和宿主两者在持续的利用和较量中完成疾病的发生和痊愈等。其次,不断发现的病毒受体、结合基序、致病因子及宿主细胞的多种免疫调节因子将成为相关领域新的研究内容。综上,开发高效安全疫苗、增强自身免疫力及利用RNAi直接抑制病毒RNA等便成为现代FMDV防治的主要内容。