朊病毒(Prion)——新的传染性病原体

朊病毒(或其类似物)能引起诸如牛海绵状脑病,绵羊痒病,传染性水貂脑病,麋、骡、鹿的慢性萎缩病以及人类的克—雅氏综合症(CJD)、格斯特曼—斯特拉斯勒综合症(GSS)及库鲁病,是一种新的传染性病原体。     

研究人员建立传染性朊病毒疾病小鼠模型

一个国际科学家小组建立了一种传染性朊病毒疾病小鼠模型。研究人员发现,通过改变两个核酸改变朊蛋白结构可以导致一种致命性的神经系统疾患。该研究的目的是研究可以引起慢性消耗性疾病即在鹿和麋鹿发现的传染性朊病毒疾病的朊蛋白变化。这种疾病与牛的牛海绵状脑病和人的Creutzfeldt-Jakob病类似。通过改变朊病毒基因中的两个核酸,     

朊病毒的研究进展

朊病毒（Prion）是一种不含核酸的蛋白浸染因子,主要引起人和动物中枢神经疾病，即传染性海绵状脑病（TSE）。目前，由其引起的朊病毒病在世界多国发生，危害严重，经济损失巨大，并对人类健康构成很大威胁.本文就朊病毒的研究历史、朊病毒蛋白、朊病毒复制及其致病机理作了综述,并提出朊病毒研究中拟待解决的问题，以期为该类疾病的防治提供理论基础及依据。     

家畜海绵状脑病和痒病的发生与诊治

传染性海绵状脑病是由朊病毒引起人和动物的某组致死性中枢神经系统变性传染病,包括牛海绵状脑病、痒病、貂传染性脑病和人的克一雅氏病、库鲁病等。家畜共同特征是潜伏期长,可达几个月至几十年,进行性共济失调,震颤,姿势不稳,知觉过敏,家畜痴呆等神经症状,病程发展缓慢,但全部以死亡告终。     

海绵状脑病研究进展

<正>朊病毒又称"蛋白质侵染因子"(一种传染源),是一类能侵染动物并在宿主细胞内复制的小分子无免疫性疏水蛋白质,它可以引起人类和其他哺乳类动物致命性脑病。目前,很多学者对正常蛋白转化成朊病毒的途径进行研究。有的学者试图通过对大鼠的研究,获得更多关于可传染的海绵状脑病(TSEs)的知识。     

牛海绵状脑病的防治

<正>牛海绵状脑病通常称为"疯牛病",是一种慢性致死性的疾病,其不仅能感染牛,还对人具有易感性。牛海绵状脑病是由朊病毒感染后引起的一种传染性疾病。牛在发病后主要表现为精神失常、行走不稳和感觉异常敏感等,最后导致病牛死亡。这不仅给养牛业带来巨大的养殖风险,还给养殖场带来较大的经济损失。本病主要通过给牛饲喂含有BSE病原的     

朊病毒及生态学意义

朊病毒(Prion)是1982年美国生理学家Prusiner及其同事在大量实验的基础上,突破经典病毒学理论而提出的〔1〕,认为绵羊瘙痒病的病原体是一种尚未证实有核酸结构的蛋白质侵染颗粒,将其称为朊病毒蛋白(Prion),简称PrP,其传染性高,抵抗力强,可引起人和动物的传染性神经退行性疾病(T     

几种新的动物及动物与人共患病简介（一）

疯牛病 1 概念：“疯牛病”有多种名称，目前世界上广泛采用的病名是“传染性海绵状脑病”（TranSmissible spongifolm encephaiopathies TSE），简称“牛海绵状脑病”（BSE）。由于它是由“朊病毒”（又称“朊粒”）引起，所以，有的又叫“朊病毒病”或“朊粒病”（Prion diseases）。除此之外还有称为“传染性变性脑病”（TDE）、“传染性脑淀粉样变性”（TCA）、“亚急性海绵状脑病”（SSE）、“亚急性海绵状病毒性脑病”（SSVE）等的。严格意义上的“TSEs”应译为“可传递性海绵状脑病”。该病是人和动物共患、呈亚急性、渐进…     

“疯牛病”浅说

牛海绵状脑病 (ＢＳＥ)俗称“疯牛病” ,是传染性海绵状脑病的一种。是一种特殊病毒———朊病毒引起人和动物的一组具有共同特征的非炎性、亚急性、渐进性、致死性中枢神经系统变性的疾病 ,故又称朊病毒病。自从 2 0世纪 80年代英国出现疯牛病以来 ,已在欧洲一些国家扩大流行 ,引起世界各国的恐慌和关注。我国虽未发现疯牛病 ,但为了预防疯牛病的发生 ,笔者将有关知识简述如下。1　疯牛病的病因是由有传染性海绵状脑病的一种即绵羊、山羊痒病病羊的骨、肉被加工成粉 ,作为牛的饲料添加剂进入牛的饲料中 ,这种痒病羊的骨肉粉中间含一种特殊…     

朊病毒检测方法综述

传染性海绵状脑病(transmissible spongiform encephalopathies,TSEs)是由朊病毒引起的人和多种哺乳动物以神经退行性变化为主要特征的一种慢性消耗性传染病,也称作朊病毒病;其是由体内正常细胞表面的PrP^C转变成PrP^Sc蛋白所导致。但PrP^Sc主要在脑内表达,在其他组织表达量很低,因此快捷准确的诊断方法对于该病有重要意义。作者重点介绍以朊病毒的致病特点为依据建立的检测方法,便于对该疾病的早期诊断、预防以及食品安全检测提供帮助,保障畜牧业的有序发展以及人类的健康。     

The prion hypothesis and the human prion diseases

Our understanding of the pathogenesis of the transmissible spongiform encephalopathies (TSE) has made terrific headway over the past 40 years and some scientists are even of the opinion that this group of diseases belongs to the neurodegenerative syndromes best understood. On the other hand, the investigation of TSE has led to a multitude of unexpected and surprising results and consequently has initiated impassioned discussions among scientists. Although the human forms of TSE are very rare, the wildfire-like spread of the bovine spongiform encephalopathy (BSE) raises the pressing question as to whether BSE is communicable to humans. This overview summarizes some current hypotheses about the nature of the infectious agent and about the pathogenesis of the damage of the central nervous system.     

Prion agent diversity and species barrier

Mammalian prions are the infectious agents responsible for transmissible spongiform encephalopathies (TSE), a group of fatal, neurodegenerative diseases, affecting both domestic animals and humans. The most widely accepted view to date is that these agents lack a nucleic acid genome and consist primarily of PrP(Sc), a misfolded, aggregated form of the host-encoded cellular prion protein (PrP(C)) that propagates by autocatalytic conversion and accumulates mainly in the brain. The BSE epizooty, allied with the emergence of its human counterpart, variant CJD, has focused much attention on two characteristics that prions share with conventional infectious agents. First, the existence of multiple prion strains that impose, after inoculation in the same host, specific and stable phenotypic traits such as incubation period, molecular pattern of PrP(Sc) and neuropathology. Prion strains are thought to be enciphered within distinct PrP(Sc) conformers. Second, a transmission barrier exists that restricts the propagation of prions between different species. Here we discuss the possible situations resulting from the confrontation between species barrier and prion strain diversity, the molecular mechanisms involved and the potential of interspecies transmission of animal prions, including recently discovered forms of TSE in ruminants.     

TSE eradication in small ruminants--quo vadis?

The term of 'TSE infections in small ruminants' summarises BSE as well as classical and the recently discovered atypical scrapie infections in sheep and goats.There are fundamental differences between the TSE infections in small and large ruminants. Other than in bovines the TSE pathogenesis in small ruminants implies that various peripheral tissues become infectious long before the onset of clinical symptoms. At least in sheep, classical scrapie is efficiently transmitted horizontally within affected flocks. On the other hand, BSE poses a distinctly higher zoonotic risk than scrapie. Therefore, regulatory measures for the protection of animals and humans from a BSE infection must be substantially different for large and small ruminants. While culling of the birth and feeding cohort of a BSE affected cattle is considered to be effective to prevent any further BSE cases in the affected herd, an effective BSE and classical scrapie eradication programme in small ruminants requires a much more stringent eradication strategy and the rendering of all susceptible animals. The situation became even more complicated when atypical scrapie cases with divergent transmission and pathogenesis characteristics and with a novel biochemical phenotype of the infectious agent came into play. The discovery of these atypical scrapie cases has initiated a discussion about the suitability of the current TSE eradication measures in sheep (which are selective breeding and genotype based culling), in particular when such cases were also found in sheep carrying the believed scrapie resistant genotypes.     

Detergents modify proteinase K resistance of PrP Sc in different transmissible spongiform encephalopathies (TSEs)

Prion diseases are diagnosed by the detection of their proteinase K-resistant prion protein fragment (PrP(Sc)). Various biochemical protocols use different detergents for the tissue preparation. We found that the resistance of PrP(Sc) against proteinase K may vary strongly with the detergent used. In our study, we investigated the influence of the most commonly used detergents on eight different TSE agents derived from different species and distinct prion disease forms. For a high throughput we used a membrane adsorption assay to detect small amounts of prion aggregates, as well as Western blotting. Tissue lysates were prepared using DOC, SLS, SDS or Triton X-100 in different concentrations and these were digested with various amounts of proteinase K. Detergents are able to enhance or diminish the detectability of PrP(Sc) after proteinase K digestion. Depending on the kind of detergent, its concentration - but also on the host species that developed the TSE and the disease form or prion type - the detectability of PrP(Sc) can be very different. The results obtained here may be helpful during the development or improvement of a PrP(Sc) detection method and they point towards a detergent effect that can be additionally used for decontamination purposes. A plausible explanation for the detergent effects described in this article could be an interaction with the lipids associated with PrP(Sc) that may stabilize the aggregates.     

Transmissible spongiform encephalopathies (TSE): old diseases with new explosive force

In view of the first 64 BSE cases (date: 11.5.01) in German cattle herds an overview on TSE and their similarities and differences regarding clinic, pathogenesis and pathology is given. The mechanism of the unconventional agent, an infectious protein (prion), is explained based on the prion model of Stanley Prusiner. The knowledge on transmission, incubation time, host specificity as well as resistance and immunity drawn from experimentally infected animals is discussed. Thus, after oral infection prions are transported by lymphocytes from the stomach-intestinal tract to the spleen. The way to the CNS is still unknown. The presumption for crossing the species barrier is twofold: first the prions of different species have to be biochemically homologous and a genetical disposition has to exist. This is the case for BSE and the new variant of Creutzfeldt-Jakob-Disease (vCJD). There is evidence that in Great Britain so far 97 (date: 30.3.01) young people acquired vCJD due to consumption of food that contained bovine risk material. Regarding the infectious prion dosis brain, spinal cord and lymphoid tissues are regarded to be most dangerous. The principle of the BSE-test, its evidence as well as steps for prevention and control of BSE are presented.     

PrP genetics in ruminant transmissible spongiform encephalopathies

Scrapie, bovine spongiform encephalopathy (BSE), and chronic wasting disease (CWD) are prion diseases in ruminants with considerable impact on animal health and welfare. They can also pose a risk to human health and control is therefore an important issue. Prion protein (PrP) genetics may be used to control and eventually eradicate animal prion diseases. The PrP gene in sheep and other representatives of the order Artiodactyles has many polymorphisms of which several are crucial determinants of susceptibility to prion diseases, also known as transmissible spongiform encephalopathies (TSE). This review will present the current understanding of PrP genetics in ruminants highlighting similarity and difference between the species in the context of TSE.     

Experimental transmission of scrapie agent to susceptible sheep by intralingual or intracerebral inoculation

Scrapie, a transmissible spongiform encephalopathy (TSE), is a naturally occurring fatal neurodegenerative disease of sheep and goats. This study documents survival periods, pathological findings, and the presence of abnormal prion protein (PrP(Sc)) in genetically susceptible sheep inoculated with scrapie agent. Suffolk lambs (AA/RR/QQ at codons 136, 154, and 171, respectively) aged 4 mo were injected by the intralingual (IL) or intracerebral (IC) route with an inoculum prepared from a pool of scrapie-affected US sheep brains. The animals were euthanized when advanced clinical signs of scrapie were observed. Spongiform lesions in the brain and PrPsc deposits in the central nervous system (CNS) and lymphoid tissues were detected by immunohistochemical and Western blot (WB) testing in all the sheep with clinical prion disease. The mean survival period was 18.3 mo for the sheep inoculated by the IL route and 17.6 mo for those inoculated by the IC route. Since the IC method is occasionally associated with anesthesia-induced complications, intracranial hematoma, and CNS infections, and the IL method is very efficient, it may be more humane to use the latter. However, before this method can be recommended for inoculation of TSE agents, research needs to show that other TSE agents can also transmit disease via the tongue.     

Propagation of scrapie in peripheral nerves after footpad infection in normal and neurotoxin exposed hamsters

As is known from various animal models, the spread of agents causing transmissible spongiform encephalopathies (TSE) after peripheral infection affects peripheral nerves before reaching the central nervous system (CNS) and leading to a fatal end of the disease. The lack of therapeutic approaches for TSE is partially due to the limited amount of information available on the involvement of host biological compartments and processes in the propagation of the infectious agent. The in vivo model presented here can provide information on the spread of the scrapie agent via the peripheral nerves of hamsters under normal and altered axonal conditions. Syrian hamsters were unilaterally footpad (f.p.) infected with scrapie. The results of the spatiotemporal ultrasensitive immunoblot-detection of scrapie-associated prion protein (PrP(Sc)) in serial nerve segments of both distal sciatic nerves could be interpreted as a centripetal and subsequent centrifugal neural spread of PrP(Sc) for this route of infection. In order to determine whether this propagation is dependent on main components in the axonal cytoskeleton (e.g. neurofilaments, also relevant for the component ;a' of slow axonal transport mechanisms), hamsters were treated -in an additional experiment- with the neurotoxin beta,beta-iminodiproprionitrile (IDPN) around the beginning of the scrapie infection. A comparison of the Western blot signals of PrP(Sc) in the ipsilateral and in the subsequently affected contralateral sciatic nerve segments with the results revealed from IDPN-untreated animals at preclinical and clinical stages of the TSE disease, indicated similar amounts of PrP(Sc). Furthermore, the mean survival time was unchanged in both groups. This in vivo model, therefore, suggests that the propagation of PrP(Sc) along peripheral nerves is not dependent on an intact neurofilament component of the axonal cytoskeleton. Additionally, the model indicates that the spread of PrP(Sc) is not mediated by the slow component ;a' of the axonal transport mechanism.     

Survey of cattle in northeast Colorado for evidence of chronic wasting disease: geographical and high-risk targeted sample.

A geographically targeted survey of potentially high-risk, adult cattle in chronic wasting disease (CWD)-endemic areas in Colorado was initiated to assess the possibility of the spread of CWD from deer to cattle under natural conditions. Surveyed cattle were sympatric with free-roaming deer in geographically defined areas where CWD occurs and where CWD prevalence has been estimated. To qualify for inclusion in the survey, cattle had to be at least 4 years old and had to have spent a minimum of 4 years in surveyed areas. Brains from culled cattle were examined microscopically and immunohistochemically for tissue alterations indicative of a transmissible spongiform encephalopathy (TSE). Two hundred sixty-two brains were suitable for evaluation and were found to lack changes indicative of a TSE infection. Prion deposition was not demonstrable using a method involving formic acid and proteinase-K treatment before application of monoclonal antibody to bovine prion protein (F99/97.6.1). Some incidental neuropathologic changes unrelated to those of TSEs were detected. Findings from this study suggest that large-scale spread of CWD from deer to cattle under natural range conditions in CWD-endemic areas of northeast Colorado is unlikely.