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Chicken type I interferons (type I IFNs) are key antiviral players of the chicken immune system and mediate the first line of defense against viral pathogens infecting the avian species. Recognition of viral pathogens by specific pattern recognition receptors (PRRs) induce chicken type I IFNs expression followed by their subsequent interaction to IFN receptors and induction of a variety of IFN stimulated antiviral proteins. These antiviral effectors establish the antiviral state in neighboring cells and thus protect the host from infection. Three subtypes of chicken type I IFNs; chIFN-α, chIFN-β, and a recently discovered chIFN-κ have been identified and characterized in chicken. Chicken type I IFNs are activated by various host cell pathways and constitute a major antiviral innate defense in chicken. This review will help to understand the chicken type 1 IFNs, host cellular pathways that are involved in activation of chicken type I IFNs and IFN stimulated antiviral effectors along with the gaps in knowledge which will be important for future investigation. These findings will help us to comprehend the role of chicken type I IFNs and to develop different strategies for controlling viral infection in poultry. 相似文献
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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。 相似文献
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Robert-Tissot C Rüegger VL Cattori V Meli ML Riond B Gomes-Keller MA Vögtlin A Wittig B Juhls C Hofmann-Lehmann R Lutz H 《Veterinary immunology and immunopathology》2011,143(3-4):269-281
The innate immune system plays a central role in host defence against viruses. While many studies portray mechanisms in early antiviral immune responses of humans and mice, much remains to be discovered about these mechanisms in the cat. With the objective of shedding light on early host-virus interactions in felids, we have developed 12 real-time TaqMan(?) qPCR systems for feline genes relevant to innate responses to viral infection, including those encoding for various IFNα and IFNω subtypes, IFNβ, intracellular antiviral factor Mx, NK cell stimulator IL-15 and effectors perforin and granzyme B, as well as Toll-like receptors (TLRs) 3 and 8. Using these newly developed assays and others previously described, we measured the relative expression of selected markers at early time points after viral infection in vitro and in vivo. Feline embryonic fibroblasts (FEA) inoculated with feline leukemia virus (FeLV) indicated peak levels of IFNα, IFNβ and Mx expression already 6h after infection. In contrast, Crandell-Rees feline kidney (CrFK) cells inoculated with feline herpes virus (FHV) responded to infection with high levels of IFNα and IFNβ only after 24h, and no induction of Mx could be detected. In feline PBMCs challenged in vitro with feline immunodeficiency virus (FIV), maximal expression levels of IFNα, β and ω subtype genes as well as IL-15 and TLRs 3, 7 and 8 were measured between 12 and 24h after infection, whereas expression levels of proinflammatory cytokine gene IL-6 were consistently downregulated until 48h post inoculation. A marginal upregulation of granzyme B was also observed within 3h after infection. In an in vivo experiment, cats challenged with FIV exhibited a 2.4-fold increase in IFNα expression in blood 1 week post infection. We furthermore demonstrate the possibility of stimulating feline immune cells in vitro with various immune response modifiers (IRMs) already known for their immunostimulatory properties in mice and humans, namely Poly IC, Resiquimod (R-848) and dSLIM?, a synthetic oligonucleotide containing several unmethylated CpG motifs. Stimulation of feline PBMCs with dSLIM? and R-848 effectively enhanced expression of IFNα within 12h by factors of 6 and 12, respectively, and Poly IC induced an increase in Mx mRNA expression of 28-fold. Altogether, we describe new molecular tools and their successful use for the characterization of innate immune responses against viruses in the cat and provide evidence that feline cells can be stimulated by synthetic molecules to enhance their antiviral defence mechanisms. 相似文献
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为探索干扰素诱导跨膜蛋白1（interferon-inducible transmembrane protein 1,IFITM1）对猪源冠状病毒复制的影响,本研究选用猪传染性胃肠炎病毒（Transmissible gastroenteritis virus,TGEV）高致病毒株及其宿主细胞PK15作为研究对象。正常PK15细胞接种TGEV后,实时荧光定量PCR检测感染后不同时间点PK15细胞中一些干扰素刺激基因（interferon-stimulated genes,ISGs）的mRNA表达水平;利用慢病毒表达系统构建稳定表达和稳定干扰IFITM1表达的PK15细胞系。将一段靶向干扰猪源IFITM1的shRNA序列及猪源IFITM1全长,分别插入pLKO.1-EGFP-Puro载体及pLVML-Myc-MCS-IRES-Puro载体中,分别构建出pLKO.1-IFITM1shRNA-EGFP-Puro及pLVML-Myc-IFITM1-IRES-Puro重组质粒。将重组质粒与慢病毒包装质粒共转染293FT细胞后获得带有目的基因的重组慢病毒,慢病毒侵染PK15细胞后用嘌呤霉素进行筛选,获得稳定表达及稳定干扰IFITM1表达的PK15细胞系,分别命名为PK15-IFITM1及PK15-IFITM1-/-,并分别用实时荧光定量PCR、间接免疫荧光试验（IFA）及Western blotting检测IFITM1干扰效率及表达情况;TGEV接种PK15-IFITM1-/-和PK15-IFITM1,实时荧光定量PCR测定细胞中TGEV的拷贝数。结果显示,PK15细胞接种TGEV后的48 h内,一些ISGs的mRNA水平均有所上升;PK15-IFITM1-/-细胞系的干扰效率为70%,PK15-IFITM1细胞系表达成功;在PK15-IFITM1-/-细胞系中,IFITM1的mRNA水平显著下调,促进了TGEV的复制。反之,在PK15-IFITM1细胞系中,TGEV的复制受到了抑制。但IFITM1的表达或缺失却不影响TGEV对PK15的吸附作用。总之,IFITM1对TGEV有显著的抗病毒作用,IFITM1不影响TGEV对PK15细胞的早期吸附,这为后续IFITM1抗冠状病毒机制的研究奠定了基础。 相似文献
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Watanabe C Uchida Y Ito H Ito T Saito T 《Veterinary immunology and immunopathology》2011,144(3-4):187-199
Highly pathogenic avian influenza virus (HPAIV) induces acute disease in chickens causing high mortality and morbidity and is a major threat to poultry industries in Southeast Asian countries. The mechanisms of disease manifestation and host innate immune responses against HAPIV in chickens are not well understood. In this study, we examined virus replication and host gene expressions in four chicken cell lines in vitro to elucidate the impact of host innate immune responses against viral replication. It was demonstrated that viral replication efficiencies were different depending on the cell line. The viral replication appeared to be affected by the basal expression of IFN related genes. The expression of immune-related genes against the viral infection also varied in a cell line dependent manner. In non-immune derived cell lines, but not in immune derived cell lines, the expression of the CCL5 and CCL20 genes were induced by HPAIV infection. Reverse genetics HPAIV, with internal genes from avirulent avian influenza, reduced virus replication and affected immune-related gene expression in a cell line dependent manner. These results suggest the possibility that differential immune responses in different cell types in local tissues could modulate the consequences of HPAIV infection in chickens. 相似文献
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为了解干扰素（interferon，IFN）和干扰素刺激基因在禽呼肠孤病毒（ARV）感染DF1细胞后的表达情况，试验将ARV病毒感染DF1细胞，观察细胞病变，收集感染后0、6、12、24、36、48、72、96 h的细胞样品，抽提反转录成cDNA，通过实时荧光定量PCR技术检测干扰素IFN-α和IFN-β及9种禽源常见干扰素刺激基因在感染后不同时间点在转录水平表达量的动态变化规律。结果显示，在ARV感染DF1细胞后，DF1细胞出现典型的细胞病变，感染后12 h病毒开始快速增殖，在36~96 h维持在较高的水平；IFN-α和IFN-β在转录水平的表达量在感染后均表现为显著下调（P<0.05；P<0.01）；IFI6、OAS、IFIT5、ISG12在转录水平表达量变化规律相似，均呈现显著上调表达（P<0.05；P<0.01），在感染后96 h达到峰值；其中IFIT5的上调幅度最大，感染后96 h的表达量是0 h的19.62倍（P<0.01）；而Mx、IFITM3、PKR、Viperin、ZAP的表达量变化规律相似，均表现为显著下调表达（P<0.05；P<0.01），其中Mx、IFITM3、Viperin的下调幅度较大，PKR和ZAP下调幅度很小。说明在ARV感染DF1细胞后，干扰素及多种干扰素刺激基因在转录水平呈现规律性变化，与病毒在DF1细胞中复制存在一定的联系。结果表明，ARV感染后可以诱导多种干扰素刺激基因的表达，这些干扰素刺激基因在抵御ARV病毒的入侵，抑制ARV的复制、释放及病毒的清除中发挥着重要作用。本研究为今后深入研究ARV的致病机理和宿主的抗病毒免疫应答提供了参考。 相似文献
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Omatsu T Bak EJ Ishii Y Kyuwa S Tohya Y Akashi H Yoshikawa Y 《Veterinary immunology and immunopathology》2008,124(1-2):169-176
Bats are considered to be natural reservoirs for several viruses of clinical importance, including rabies virus, Nipah virus, and Hendra virus. Type I interferons (IFNs) is an important part of the immune system in the defense against viral infection. To investigate the function of type I IFNs upon viral infection in bats, the nucleic acid, and amino acid sequences of Egyptian Rousette (Rousettus aegyptiacus) IFN-alpha and -beta were characterized. Sequence data indicated that bat IFN-alpha consists of 562-bp encoded 187-aa, and IFN-beta consisted of 558-bp encoded 186-aa. Phylogenetic analysis of the overall identity of IFN-beta shared the highest sequence homology with pig IFN-beta in both nucleotide and amino acid level. Stimulation of bat primary kidney cells (BPKCs) and bat lung cell lines, Tb-1 Lu, with polyinosinic-polycytidylic acid (poly(I:C)) or exogenous bat type I IFNs resulted in increased type I IFNs mRNA expression in BPKCs, but not in Tb-1 Lu. Characterization of the bat IFN-alpha and -beta genes allows understanding of the immune responses upon stimulation in different tissues, thus providing practical strategies for control and treatment of clinically important diseases. These results are important especially for the virus infection, and suggest that future molecular studies on virus infection experiment of bats in vitro will require careful consideration of the differences of type I IFN expression patterns in different cell types. 相似文献
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Recombinant porcine interferon gamma (rPoIFN gamma) induced a dose-dependent inhibition of the cytopathic effect produced by vesicular stomatitis virus (VSV) challenge of both homologous and heterologous (bovine) cell lines. In addition, an antiviral effect of rPoIFN gamma was demonstrable against the coronavirus transmissible gastroenteritis virus (TGEV) infection of porcine epithelial cells and of pulmonary macrophages. A rabbit anti-PoIFN gamma antiserum was prepared and shown to specifically neutralize the antiviral effects of natural and recombinant porcine IFN gamma preparations. This antiserum could also neutralize recombinant bovine IFN gamma but not recombinant human IFN gamma. These results suggest antigenic homology of porcine and bovine IFN gamma but antigenic differences between these molecules and human IFN gamma. 相似文献
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很多宿主细胞在病毒感染下通常会启动caspases通路凋亡途径导致细胞死亡,避免病毒的进一步扩增和传播.但最近的一些研究表明,病毒能利用激活的caspase蛋白酶对自身(非)结构蛋白进行特异性剪切,以利于病毒在细胞内的复制或参与病毒或宿主其他基因的转录调控等过程.作为一个病毒与宿主细胞相互作用关系的新的研究领域,论文对... 相似文献
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E A Hoover J I Mullins 《Journal of the American Veterinary Medical Association》1991,199(10):1287-1297
Feline leukemia virus is a naturally occurring, contagiously transmitted and oncogenic immunosuppressive retrovirus of cats. The effects of FeLV are paradoxical, causing cytoproliferative and cytosuppressive disease (eg, lymphoma and myeloproliferative disorders vs immunodeficiency and myelosuppressive disorders). In the first few weeks after virus exposure, interactions between FeLV and hemolymphatic system cells determine whether the virus or the cat will dominate in the host/virus relationship--persistent viremia and progressive infection or self limiting, regressive infection will develop. The outcome of these early host/virus interactions is revealed in the diagnostic assays for FeLV antigenemia and viremia. The latter, in turn, predict the outcome of FeLV infection in cats. Known host resistance factors include age and immune system functional status. Known virus virulence factors are magnitude of exposure and virus genotype. Molecular analysis of FeLV strains indicated that natural virus isolates exist as mixtures of closely related virus genotypes and that minor genetic variations among FeLV strains can impart major differences in pathogenicity. The genetic coding regions responsible for cell targeting and specific disease inducing capacity (eg, thymic lymphoma, acute immunosuppression, or aplastic anemia) have been mapped to the virus surface glycoprotein and/or long terminal repeat regions for several FeLV strains. Infection by specific FeLV strains leads to either malignant transformation or cytopathic deletion of specific lymphocyte and hemopoietic cell population, changes that prefigure the onset of clinical illness. Another notable feature of the biology of FeLV is that many cats are able to effectively contain and terminate viral replication, an important example of host immunologic control of a retrovirus infection and a process that can be selectively enhanced by vaccination. Thus, FeLV infection serves as a natural model of the multifaceted pathogenesis of retroviruses and as a paradigm for immunoprophylaxis against an immunosuppressive leukemogenic retrovirus. 相似文献
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Karalyan Z Zakaryan H Sargsyan Kh Voskanyan H Arzumanyan H Avagyan H Karalova E 《Veterinary immunology and immunopathology》2012,145(1-2):551-555
African swine fever virus (ASFV) is the causative agent of African swine fever that is the significant disease of domestic pigs, with high rates of mortality. ASFV is double-stranded DNA virus whose genes encode some proteins that are implicated in the suppression of host immune response. In this study, we have modeled in vivo infection of ASFV for determination of interferon (IFN) status in infected pigs. We measured the level of IFN-α, -β and -γ by enzyme-linked immunosorbent assay and showed that the level of IFN-α sharply decreased during infection. Unlike IFN-α, the level of IFN-β and -γ increased from the 2nd and 4th days post-infection, respectively. Also, we analyzed the population dynamics of peripheral white blood cells of infected pigs due to their important role in host immune system. We showed that the atypical lymphocytes appeared after short time of infection and this result is in accordance with our previous study done in vitro. At the last day of infection about 50% of the total white blood cells were destroyed, and the remaining cells were represented mainly by small-sized lymphocytes, reactive lymphocytes and lymphoblasts. 相似文献
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Raj Kumar Singh Muthannan Andavar Ramakrishnan Kumaragurubaran Karthik Rekha Khandia 《The Veterinary quarterly》2017,37(1):98-135
Ebola virus (EBOV) is an extremely contagious pathogen and causes lethal hemorrhagic fever disease in man and animals. The recently occurred Ebola virus disease (EVD) outbreaks in the West African countries have categorized it as an international health concern. For the virus maintenance and transmission, the non-human primates and reservoir hosts like fruit bats have played a vital role. For curbing the disease timely, we need effective therapeutics/prophylactics, however, in the absence of any approved vaccine, timely diagnosis and monitoring of EBOV remains of utmost importance. The technologically advanced vaccines like a viral-vectored vaccine, DNA vaccine and virus-like particles are underway for testing against EBOV. In the absence of any effective control measure, the adaptation of high standards of biosecurity measures, strict sanitary and hygienic practices, strengthening of surveillance and monitoring systems, imposing appropriate quarantine checks and vigilance on trade, transport, and movement of visitors from EVD endemic countries remains the answer of choice for tackling the EBOV spread. Herein, we converse with the current scenario of EBOV giving due emphasis on animal and veterinary perspectives along with advances in diagnosis and control strategies to be adopted, lessons learned from the recent outbreaks and the global preparedness plans. To retrieve the evolutionary information, we have analyzed a total of 56 genome sequences of various EBOV species submitted between 1976 and 2016 in public databases. 相似文献
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禽流感病毒非结构蛋白的研究进展 总被引：1，自引：0，他引：1
流感病毒含8个负链单股独立的RNA片段,共编码10种蛋白。每种蛋白具有不同的结构和功能。其中NS基因合成NS1和NS2两种蛋白质,NS1为非结构蛋白,NS2为结构蛋白,这两种蛋白质大量存在于感染的细胞中。NS1蛋白在病毒转录及感染过程中起重要作用,与禽流感病毒的致病性密切相关,其主要功能是以多种方式解除宿主干扰素防御系统。随着分子生物技术的快速发展,关于NS1蛋白在禽流感病毒致病性方面的作用的研究也取得了一定的进展。文章主要对流感病毒NS基因的特点及其编码蛋白质功能进行综述。 相似文献
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《Veterinary microbiology》2015,175(2-4):232-243
Muscovy duck reovirus (MDRV) is a highly pathogenic virus in waterfowl and causes significant economic loss in the poultry industry worldwide. Because the host innate immunity plays a key role in defending against virus invasion, more and more attentions have been paid to the immune response triggered by viral infection. Here we found that the genomic RNA of MDRV was able to rapidly induce the production of interferons (IFNs) in host. Mechanistically, MDRV infection induced robust expression of IFNs in host mainly through RIG-I, MDA5 and TLR3-dependent signaling pathways. In addition, we observed that silencing VISA expression in 293T cells could significantly inhibit the secretion of IFNs. Remarkably, the production of IFNs was reduced by inhibiting the activation of NF-κB or knocking down the expression of IRF-7. Furthermore, our study showed that treatment of 293T cells and Muscovy duck embryo fibroblasts with IFNs markedly impaired MDRV replication, suggesting that these IFNs play an important role in antiviral response during the MDRV infection. Importantly, we also detected the induced expression of RIG-I, MDA5, TLR3 and type I IFN in Muscovy ducks infected with MDRV at different time points post infection. The results from in vivo studies were consistent with those in 293T cells infected with MDRV. Taken together, our findings reveal that the host can resist MDRV invasion by activating innate immune response involving RIG-I, MDA5 and TLR3-dependent signaling pathways that govern IFN production. 相似文献
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Antonio Alcamí Geoffrey L. Smith 《Comparative immunology, microbiology and infectious diseases》1996,19(4):305-317
Poxviruses encode a broad range of proteins that counteract the formidable attack of the immune response initiated in the host after infection, among which are proteins that mimic the extracellular binding domain of host cytokine receptors and are secreted from virus-infected cells. A soluble interferon-γ receptor (IFN-γR) is produced early after infection and efficiently blocks the binding of IFN-γ to cellular receptors, thus inhibiting both the anti-viral and immune functions of IFN-γ. An IFN-γR is highly conserved among members of the poxvirus family, suggesting a major role in viral pathogenesis. The highly species-specific nature of the IFN system enables questions concerning the evolutionary relationship between poxviruses and their hosts to be addressed. The IFN-γR encoded by myxoma virus, a natural pathogen of rabbits, is specific for rabbit IFN-γ. However, the IFN-γR encoded by orthopoxviruses (vaccinia, cowpox, camelpox, ectromelia) shows a novel, broad species specificity suggesting that these viruses have evolved in several species. The implications for the unknown origin and natural host(s) of vaccinia virus are discussed. 相似文献
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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。 相似文献
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Myxoma virus (MV) is a poxvirus that evolved in Sylvilagus lagomorphs, and is the causative agent of myxomatosis in European rabbits (Oryctolagus cuniculus). This virus is not a natural pathogen of O. cuniculus, yet is able to subvert the host rabbit immune system defenses and cause a highly lethal systemic infection. The interaction of MV proteins and the rabbit immune system has been an ideal model to help elucidate host/poxvirus interactions, and has led to a greater understanding of how other poxvirus pathogens are able to cause disease in their respective hosts. This review will examine how MV causes myxomatosis, by examining a selection of the identified immunomodulatory proteins that this virus expresses to subvert the immune and inflammatory pathways of infected rabbit hosts. 相似文献