Animal models of henipavirus infection: A review

Hendra virus (HeV) and Nipah virus (NiV) form a separate genus Henipavirus within the family Paramyxoviridae, and are classified as biosafety level four pathogens due to their high case fatality rate following human infection and because of the lack of effective vaccines or therapy. Both viruses emerged from their natural reservoir during the last decade of the 20th century, causing severe disease in humans, horses and swine, and infecting a number of other mammalian species. The current review summarises current published data relating to experimental infection of small and large animals, including the natural reservoir species, the Pteropus bat, with HeV or NiV. Susceptibility to infection and virus distribution in the individual species is discussed, along with the pathogenesis, pathological changes, and potential routes of transmission.     

尼帕病毒研究进展

尼帕病毒(Nipah virus,NiV)是新近发现的引发脑部炎症或呼吸道疾病等重症的新型人畜共患病病毒,该病毒最初于1999年马来西亚尼帕镇的1名脑炎患者脑脊液中分离获得,至今已经历了数次大的流行,造成严重的经济损失和人员伤亡.该病毒可由动物传播给人,也可直接人与人传播,并且能够在猪等动物身上引起严重疾病,狐蝠科的果蝠是该病毒的天然宿主.NiV感染人后的病死率极高,并且目前还没有有效的疫苗和治疗措施,生物危害性极大,被列为生物安全4级病原(BSL4).笔者从NiV的分类及分型、基因和蛋白质组、流行和分布、疫苗研制、临床和病理变化以及实验室诊断技术等方面对NiV做简单的概述.     

尼帕病毒病及其病原的研究进展

概述了尼帕病毒病在国外的流行状况、尼帕病毒（Nipah virus，NiV）的变异及我国的研究现状，着重阐述了近年来在其基础病毒学、诊断技术及防治方面的研究进展，主要包括病毒蛋白的功能及其相互作用、受体的发现、动物模型、荧光PCR及ELISA诊断技术、抑制NiV感染及治疗等方面的研究成果，为该病的深入研究提供了参考。     

Serological examination for evidence of infection with Hendra and Nipah viruses in Queensland piggeries

OBJECTIVE: To examine piggeries in Queensland for evidence of infection with Hendra virus and Nipah virus. DESIGN: A serological survey was designed to provide 99% confidence of detecting at least one infected pig herd in Queensland, assuming that for each virus, at least 5% of herds would have been exposed to virus and that at least 40% of the finisher pigs in these herds would have detectable antibodies to virus. PROCEDURE: A two stage sampling regimen was used. All samples were tested with serum neutralisation tests developed and performed at the Australian Animal Health Laboratory. RESULTS: There was no evidence of antibody to either virus in the 500 samples collected from 100 herds. CONCLUSION: The results of the survey support a case that commercial pigs in Queensland are free of both Hendra virus and Nipah virus infections.     

尼帕病毒检测技术研究进展

尼帕病毒（Nipah virus, NiV）是一种人畜共患的高致病性病毒，人感染NiV后，死亡率接近40%；猪作为中间宿主，感染NiV后具有高发病率和高死亡率特点。近年来，NiV疫情在我国相邻的多个东南亚国家频繁出现，预示该病传入我国风险日益增高。本研究阐述了近年来NiV在血清学诊断和分子学诊断技术方面的研究进展，包括临床常用的传统技术，以及重组蛋白ELISA、Luminex、二代测序等新兴诊断方法，为临床样本中NiV的鉴定和监测方法更新换代提供参考，对监测NiV从国外的传入情况、防控猪群NiV疫情发生以及守护公共卫生安全具有重大意义。     

尼帕病毒流行病学研究进展

尼帕病是由副黏病毒科中的尼帕病毒引起的新型烈性人畜共患传染病,其严重威胁人类与猪等动物的健康。作者就尼帕病毒的病原学特征、流行病学和临床症状等进行了概述,以期初步了解尼帕病毒。     

Hendra and Nipah virus infections.

The most important clinical and pathological manifestation of Hendra virus infection in horses and humans is that of severe interstitial pneumonia caused by viral infection of small blood vessels. The virus is also capable of causing nervous disease. Hendra virus is not contagious in horses and is spread by close contact with body fluids, such as froth from infected lungs. Diagnosis should be based on the laboratory examination of blood, lung, kidney, spleen, and, if nervous signs are present, also of the brain. Evidence of infection with the more recently identified and related Nipah virus was found in the brain of one horse in which there was inflammation of the meningeal blood vessels. Fruit bats, especially Pteropus s., have been incriminated as the natural and reservoir hosts of both Hendra and Nipah viruses.     

亨德拉病毒研究进展

亨德拉病毒(HeV)是属于副黏病毒科、副黏病毒亚科、亨尼病毒属的一种病毒,可引起马、人类和其他哺乳动物的感染。动物和人类感染该病毒后病死率很高,且缺乏有效的疫苗和治疗方法。不同动物的易感情况、发病机理、病理变化、潜在的传播途径等情况等仍有待进一步研究。论文就亨德拉病毒自然宿主和实验动物感染等情况进行重点阐述。     

尼帕病毒病的研究进展

尼帕病毒病是由副黏病毒科中的尼帕病毒引起的人兽共患病,它是严重危害人类与养猪业等的一种较新的重要病原。文章综述了该病主要病原学特征包括病毒的特性和功能蛋白,分析讨论了传染源、传播途径及人畜的易感性,以及人、猪、犬和猫感染后的病理变化简单描述了其致病机理、临床症状、诊断和防制措施。     

Canine distemper,a re-emerging morbillivirus with complex neuropathogenic mechanisms

Paramyxoviruses are responsible for a wide variety of diseases both in humans and in animals. Common to many paramyxoviruses is the fact that they can cause neurological symptoms in their final host. Newly discovered paramyxoviruses, such as the Hendra and Nipah viruses, show the same pattern of pathogenesis as that of the paramyxoviruses already known. Canine distemper virus (CDV) is a well-studied member of the genus Morbillivirus. Study of the neuropathogenesis of CDV might give insight into disease mechanisms and suggest approaches for the prevention of other recently discovered paramyxovirus infections.     

Nipah virus: epidemiology,pathology, immunobiology and advances in diagnosis,vaccine designing and control strategies – a comprehensive review

Nipah (Nee-pa) viral disease is a zoonotic infection caused by Nipah virus (NiV), a paramyxovirus belonging to the genus Henipavirus of the family Paramyxoviridae. It is a biosafety level-4 pathogen, which is transmitted by specific types of fruit bats, mainly Pteropus spp. which are natural reservoir host. The disease was reported for the first time from the Kampung Sungai Nipah village of Malaysia in 1998. Human-to-human transmission also occurs. Outbreaks have been reported also from other countries in South and Southeast Asia. Phylogenetic analysis affirmed the circulation of two major clades of NiV as based on currently available complete N and G gene sequences. NiV isolates from Malaysia and Cambodia clustered together in NiV-MY clade, whereas isolates from Bangladesh and India clusterered within NiV-BD clade. NiV isolates from Thailand harboured mixed population of sequences. In humans, the virus is responsible for causing rapidly progressing severe illness which might be characterized by severe respiratory illness and/or deadly encephalitis. In pigs below six months of age, respiratory illness along with nervous symptoms may develop. Different types of enzyme-linked immunosorbent assays along with molecular methods based on polymerase chain reaction have been developed for diagnostic purposes. Due to the expensive nature of the antibody drugs, identification of broad-spectrum antivirals is essential along with focusing on small interfering RNAs (siRNAs). High pathogenicity of NiV in humans, and lack of vaccines or therapeutics to counter this disease have attracted attention of researchers worldwide for developing effective NiV vaccine and treatment regimens.     

Hendra (equine morbillivirus)

Hendra has been recognized in Australia as a new zoonotic disease of horses since 1994/5 and subsequent work has shown that the viral agent is endemic in certain species of fruit bat. The Hendra virus is the type species of a new genus within the sub-family Paramyxovirinae, which also contains another newly identified zoonotic bat virus, namely Nipah. It is assumed that contact with bats has led to the Hendra virus being transferred to horses on each of the three separate incidents that have been reported in the last five years. No evidence has been found for widespread subclinical infection of horses.Infected horses can develop a severe and often fatal respiratory disease characterized by dyspnoea, vascular endothelial damage and pulmonary oedema. Nervous signs may also occur. Fatal respiratory disease has been seen in cats and guinea pigs following experimentally induced infections. Transmission of the virus from horses to other horses or man seems to have taken place, but very close contact was required. Three human cases have been recognized, all in association with equine cases. There have been two human fatalities, one due to respiratory failure and the other from a delayed-onset encephalitis. A number of diagnostic methods have been developed, but great care must be taken in obtaining samples from suspected cases.     

Experimental inoculation study indicates swine as a potential host for Hendra virus

Hendra virus (HeV) is a zoonotic virus from the family Paramyxoviridae causing fatal disease in humans and horses. Five-week-old Landrace pigs and 5-month-old Gottingen minipigs were inoculated with approximately 10⁷ plaque forming units per animal. In addition to fever and depression exhibited in all infected pigs, one of the two Landrace pigs developed respiratory signs at 5 days post-inoculation (dpi) and one of the Gottingen minipigs developed respiratory signs at 5 dpi and mild neurological signs at 7 dpi. Virus was detected in all infected pigs at 2–5 dpi from oral, nasal, and rectal swabs and at 3–5 dpi from ocular swabs by real-time RT-PCR targeting the HeV M gene. Virus titers in nasal swab samples were as high as 10^4.6 TCID₅₀/mL. The viral RNA was mainly distributed in tissues from respiratory and lymphoid systems at an early stage of infection and the presence of virus was confirmed by virus isolation. Pathological changes and immunohistochemical staining for viral antigen were consistent with the tissue distribution of the virus. This new finding indicates that pigs are susceptible to HeV infections and could potentially play a role as an intermediate host in transmission to humans.     

尼帕病毒的研究进展

尼帕病毒(Nipah virus)属副黏病毒科(paramyxoviridae),为非节段性单负链RNA病毒,因1999年首次从马来西亚尼帕镇脑炎患者的脑脊液中分离出而得名,其以高致死性为主要特征,主要侵害中枢神经系统和呼吸系统,引起急性发热、头痛和不同程度的意识障碍。其因感染的宿主广泛、疾病进展迅速、病死率极高而引起人们的高度关注。笔者对尼帕病毒的生物学特性和分子生物学特性、致病性、致病机理及实验室诊断方法进行了综述。     

No Evidence of Hendra Virus Infection in the Australian Flying‐fox Ectoparasite Genus Cyclopodia

Hendra virus (HeV) causes potentially fatal respiratory and/or neurological disease in both horses and humans. Although Australian flying‐foxes of the genus Pteropus have been identified as reservoir hosts, the precise mechanism of HeV transmission has yet to be elucidated. To date, there has been limited investigation into the role of haematophagous insects as vectors of HeV. This mode of transmission is particularly relevant because Australian flying‐foxes host the bat‐specific blood‐feeding ectoparasites of the genus Cyclopodia (Diptera: Nycteribiidae), also known as bat flies. Using molecular detection methods, we screened for HeV RNA in 183 bat flies collected from flying‐foxes inhabiting a roost in Boonah, Queensland, Australia. It was subsequently demonstrated that during the study period, Pteropus alecto in this roost had a HeV RNA prevalence between 2 and 15% (95% CI [1, 6] to [8, 26], respectively). We found no evidence of HeV in any bat flies tested, including 10 bat flies collected from P. alecto in which we detected HeV RNA. Our negative findings are consistent with previous findings and provide additional evidence that bat flies do not play a primary role in HeV transmission.     

Menangle and Nipah virus infections of pigs.

Viruses belonging to the family Paramyxoviridae generally have not been recognized as a significant cause of disease in pigs until recently. Between 1997 and 1999, there were large outbreaks of disease in pigs in Australia and Malaysia due to infection with viruses that have been shown to be new members of the Paramyxoviridae family. This article reviews current knowledge of Menangle and Nipah virus infections in pigs, the only major species of domestic animals to experience serious disease after infection with these viruses.     

亨得拉病毒核蛋白基因(N)在大肠杆菌的高效表达与反应原性鉴定

从引进的含亨得拉病毒（Hendra virus，HeV）基因的克隆质粒中扩增得到该病毒核蛋白基因（N），将其克隆到pET-28a（＋）原核表达栽体，转化大肠杆菌后成功地表达了N蛋白，SDS-PAGE电泳分析结果表明目的基因在JM109（DE3）大肠杆菌菌株中得到了良好的表达，目的蛋白量占菌体总蛋白的14．6％。Western-blotting检测表明，表达的蛋白可以被兔抗亨得拉全病毒阳性血清识别，表明该蛋白具有良好的反应性。该研究结果可进一步应用于诊断试剂和单克隆抗体的制备以及流行病学调查，以防范该病在我国的流行。     

lncRNA在猪流产相关病毒感染中的作用研究进展

猪的繁殖力是决定其生产效率的重要因素,而病毒感染导致的猪流产问题严重影响猪的繁殖效率。了解猪流产相关病毒的致病机制有助于提高猪的繁殖效率,然而大量的研究主要集中在病毒与宿主的蛋白质或基因组DNA上,近年来,长链非编码RNA （long noncoding RNA,lncRNA）从新的视角揭示了病毒与宿主的相互作用,为研究二者之间的互作关系提供了新的途径。lncRNA是一组长度>200 nt的转录本,主要通过与DNA、RNA、染色质和蛋白质互作发挥功能,在某些发育阶段、组织和疾病状态中发生特异性表达,参与机体的多种调控。lncRNA是调控病毒与宿主相互作用的关键因子,在病毒感染宿主后lncRNA发生差异性表达,对应的靶基因富集到炎症和免疫相关的信号通路,参与机体的炎症、免疫和抗病毒反应。深入了解lncRNA在猪流产相关病毒与宿主之间的调控作用,对预防和治疗病毒感染导致的猪流产具有重要意义。作者对lncRNA及其与猪流产相关病毒的关系、宿主lncRNA与病毒的互作及调控通路展开了综述,并对其存在的问题及应用前景进行了展望,以期为猪的抗病育种、猪流产药物的开发和设计及流产类相关疾病的靶点治疗等提供理论依据。     

(Highly pathogenic) avian influenza as a zoonotic agent

Zoonotic agents challenging the world every year afresh are influenza A viruses. In the past, human pandemics caused by influenza A viruses had been occurring periodically. Wild aquatic birds are carriers of the full variety of influenza virus A subtypes, and thus, most probably constitute the natural reservoir of all influenza A viruses. Whereas avian influenza viruses in their natural avian reservoir are generally of low pathogenicity (LPAIV), some have gained virulence by mutation after transmission and adaptation to susceptible gallinaceous poultry. Those so-called highly pathogenic avian influenza viruses (HPAIV) then cause mass die-offs in susceptible birds and lead to tremendous economical losses when poultry is affected. Besides a number of avian influenza virus subtypes that have sporadically infected mammals, the HPAIV H5N1 Asia shows strong zoonotic characteristics and it was transmitted from birds to different mammalian species including humans. Theoretically, pandemic viruses might derive directly from avian influenza viruses or arise after genetic reassortment between viruses of avian and mammalian origin. So far, HPAIV H5N1 already meets two conditions for a pandemic virus: as a new subtype it has been hitherto unseen in the human population and it has infected at least 438 people, and caused severe illness and high lethality in 262 humans to date (August 2009). The acquisition of efficient human-to-human transmission would complete the emergence of a new pandemic virus. Therefore, fighting H5N1 at its source is the prerequisite to reduce pandemic risks posed by this virus. Other influenza viruses regarded as pandemic candidates derive from subtypes H2, H7, and H9 all of which have infected humans in the past. Here, we will give a comprehensive overview on avian influenza viruses in concern to their zoonotic potential.     

尼帕病

本文对尼帕病的流行、病原特征、临床症状、病理特性、诊断及防制进行了概述。