戊型肝炎疫苗研究最新进展

戊型肝炎是由戊型肝炎病毒(HEV)引起的急性自限性疾病,一般不发展成慢性,但最新研究表明,在器官移植等免疫抑制人群中存在持续性HEV感染[1].HEV主要经粪口途径传播,也可经输血和母婴传播[2].HEV只有一个血清型,但其基因型主要有1～4型,基因1型和2型只感染人,而3型和4型既可感染人,也可感染多种动物.     

戊型肝炎流行病学及治疗进展

戊型肝炎 (hepatitis E)是由戊型肝炎病毒(HEV)引起的急性病毒性肝炎,主要经粪口途径传播,也有经输血传播的报道[1].HEV目前主要有7个基因型(HEV1～7)[2],其中HEV1～4与人类疾病关系最为密切.HEV1和HEV2只感染人,主要流行于卫生条件较差的发展中国家,常因水源被污染而造成大规模流行.发达国家以人畜共患的HEV3和HEV4感染引起的散发病例为主,多由摄入未煮熟的被HEV污染的动物肉类引起[1].     

实验感染戊型肝炎病毒动物模型的研究进展

根据国内外文献报道,多种动物（马、猪、牛、羊、鼠等）体内抗戊型肝炎病毒（HEV）抗体阳性,提示HEV是人兽共患病。为进一步探明HEV的动物宿主、传播方式及致病机制,本文对实验感染HEV动物模型的研究进展进行了综述。     

戊型肝炎病毒细胞培养和动物感染的研究进展

戊型肝炎(hepatitis E,HE)是一种严重危害人类健康的疾病。学者们尝试采用不同的实验方法以获取其致病因子戊型肝炎病毒(hepatitis Evirus,HEV),进而深入研究HEV的生物学特性、HEV的检测和疫苗的筛选。本文就从目前HEV细胞培养和动物感染的进展方面作一介绍。     

家猪戊型肝炎的实验感染

戊型肝炎(HE)是许多热带和亚热带国家中新出现的一种常见的急性病毒性肝炎,病原体是27～34nm的戊型肝炎病毒颗粒(HEV)。在非人类灵长目动物中已有HEV感染的实验报道,但是非灵长目脊椎动物能否感染HEV目前尚无研究和报告。为此,作者进行了这次动物实验,并获得成功。实验用HEV是从成年人HE患者排泄的粪便配制成10％的水溶液中提取的,其中所含的病毒颗粒经免疫荧光形态学鉴定和猿猴感染实验证实与HEV同质。实验动物为4头家养大白猪种的幼猪,体重8～10kg,静脉内注射1.5ml和口服2.0ml HEV提取液。另有2头幼猪接种经过中和处理的HEV     

戊型肝炎疫苗研究进展

戊型肝炎(戊肝)病毒(HEV)经粪-口途径传播,有嗜肝性,发病时表现为急性肝炎.在亚洲及非洲发展中国家均有传播,中国亦有分布.在发达国家,HEV主要影响猪和禽的养殖,密切接触生猪及鲜猪肉的人群中,抗-HEV抗体阳性率较高.虽然在发达国家仅有零星病例,但是普通人群中抗体阳性率比预期要高[1].在中亚和东南亚,HEV是急性临床型肝炎病例最主要的病原体,而在中非、东非和北非,HEV是造成肝病的第二位原因(仅次于HBV)[1].HEV感染的病死率为1%～4%[1],孕妇感染后病死率可高达20%[1,2].HEV分5个基因型,其中1、2型感染人类,3、4型可感染人和猪,5型感染鸟类[1].     

荷兰的猪HEV序列与人HEV序列相关

戊型肝炎病毒(HEV)是许多发展中国家引起肝炎的主要原因。最近,在北美和亚洲的猪中已检测到HEV,提示HEV有潜在的动物源性传播。为了调查荷兰的猪中是否普遍感染HEV,以及明确猪HEV毒株与已知的人HEV毒株的关系,作者对选自荷兰各地养猪场的115头猪和9头家养猪的粪便样本进行了研究。     

戊型肝炎食源性传播的研究进展

戊型肝炎病毒(HEV)是常见的通过粪-口途径传播的肝炎病毒,猪和鹿等动物是其主要的宿主.入食用这些动物的肉及肉制品就有感染HEV的风险,易引起急性或亚急性戊型肝炎.近年来食源性戊型肝炎流行情况严重,已经成为全球关注的公共卫生问题.此文对HEV病原学、戊型肝炎流行病学特征以及食源性传播情况进行综述,进一步了解HEV食源性传播风险,为预防和控制戊型肝炎的流行提供科学依据.     

戊型肝炎流行病学研究新进展

戊型肝炎(HE)是由戊型肝炎病毒(HEV)感染引起的急性病毒性肝炎,在全球范围广泛流行,不同基因型的HEV决定了其流行病学差异。HE的大规模暴发或流行主要见于亚洲和非洲等卫生基础条件较差的发展中国家,而发达国家以散发为主。据世界卫生组织预测全球约1/3人口有感染HEV的风险,每年约2 000万人感染HEV,并导致300万人发病,5.66万人死亡。HEV感染对人群健康造成重大威胁,尤其是老年人和孕妇。研究表明HE也是一种人畜共患疾病,猪是HEV的主要动物宿主和人类HE的主要传染源。接种疫苗是预防控制HE的重要措施,由我国自主创新研制的重组HE疫苗已于2012年10月上市启用。本文对HE流行病学研究进展进行综述,并据此提出相应的防控措施。     

戊型肝炎病毒动物宿主及跨种传播的研究进展

戊型肝炎病毒(HEV)是戊型肝炎的病原体,它是一种主要经粪-口途径传播的肝炎病毒.此文主要介绍了HEV动物宿主及其跨种传播的研究进展,为进一步研究HEV的演化和跨种传播方面提供参考.     

Phylogenetic analysis of 626 hepatitis E virus (HEV) isolates from humans and animals in China (1986-2011) showing genotype diversity and zoonotic transmission

Hepatitis E is considered as a public health problem in China. To determine the overall molecular epidemiology of hepatitis E virus (HEV) and analyze the situation of cross-species transmission between humans and swine in China over the last 25 years (1986-2011), 626 HEV complete and partial sequences (89 isolates identified by our group) isolated from humans and animals in China were retrieved from GenBank and subjected to phylogenetic analysis. There were three genotypes and 11 sub-genotypes of HEV prevailing in China. Furthermore, rabbit HEVs, of which the genotype is controversial, are also widespread in China. Genotype 1 was the most isolated genotype prior to 2000 and mainly detected in Xinjiang, Beijing and East China. However, genotype 4, which was identified in most regions of China during the last 10 years, has overtaken genotype 1 in frequency of isolation nationwide. Genotype 3 HEV strains have been found only in eastern China and were thought to be imported from Japan. Both genotypes 3 and 4 were found in humans and swine and cross-species transmission from pigs to humans of the two genotypes may have occurred in Northeast, Northwest, North, East and South China. These results indicate that HEV strains with considerable genetic diversity are widespread and the zoonotic transmission between swine and humans appears ubiquitous in China.     

The effects of synonymous codon usages on genotypic formation of open reading frames in hepatitis E virus

Hepatitis E virus (HEV) infection has emerged as an important public health issue. As a zoonotic RNA virus, new strains are continuously discovered from human or various animal species. However, the capability of cross-species infection varies largely among different strains. Because the classical nucleotide-based genotyping system provides little functional insight, this study aimed to comprehensively investigate codon usage of the HEV coding regions for better understanding the evolutional orientation, virus-host interaction and cross-species transmission. We observed significant differences of the four nucleotide usages in the three open reading frames, indicating that the evolutional tendency of HEV caused by mutation pressure is modified by the evolutional dynamic related to positive selection. Furthermore, significant differences of nucleotide usages were found among HEV isolated from different host species, suggesting an important role of natural selection related to the host. Analysis of effective number of codons revealed distinct degrees of biased codon usage caused by mutation pressure or the host. Finally, we have mapped the similarity levels of the overall codon usage between the virus and the host to assess the potential of cross-species infection. Thus, this study has provided a novel aspect for better understanding the HEV genetic orientation and the zoonotic nature.     

Hepatitis E virus infection in work horses in Egypt.

Hepatitis E virus (HEV) is an important cause of hepatitis among young Egyptian adults with high seroprevalence rates seen in both rural areas of the Nile Delta and in suburban Cairo. Because natural antibodies to HEV have been detected in animals and zoonotic transmission is postulated, we surveyed work horses in Cairo for evidence of HEV exposure and viremia. Sera from 200 Cairo work horses were tested by ELISA for the presence of IgG anti-HEV antibody revealed a seropositivity of 13%. Among 100 samples processed for detection of viral genome by means of nested polymerase chain reaction (N-PCR), 4% were positive and indicative of viremia. Viremic animals were less than 1 year old. Relative to PCR-negative horses, PCR-positive animals demonstrated significant elevation of AST (p=0.03). Phylogenetic analysis of a 253-bp fragment, in the ORF-1,2,3 overlap region of the HEV genome from the viremic animals showed that three of these viral strains to be identical, and closely related (97-100% nucleotide identity) to two human isolates from Egypt, and distant (78-96%) from 16 other HEV isolates from human and animals and shared 99.6% NI with the fourth strain. The consensus sequence of the four strains was origin obtained elsewhere. These data indicated that horses acquire HEV infection and suggest that cross-species transmission may occur. Whether horses play a role in the transmission of HEV needs further investigation.     

Comparison of hepatitis E virus genotypes from rabbits and pigs in the same geographic area: No evidence of natural cross-species transmission between the two animals

Domesticated pigs have been shown to be a reservoir of genotypes 3 and 4 hepatitis E virus (HEV). Farmed rabbits were recently recognized as the host of a novel virus, rabbit HEV. In order to determine whether HEV is transmitted naturally between rabbits and pigs, a survey on HEV infections was conducted in rabbits and pigs aged 2–4 months from rabbit and pig farms located near to each other in nine villages in three counties of Hebei Province, China. The overall anti-HEV antibody positivity rates in serum samples of swine and rabbits were 61.7% (58/94) and 23.2% (67/289), and the positive rates for HEV RNA were 23.4% (22/94) and 10% (29/289), respectively. In addition, 37 of 125 swine fecal samples (29.6%) were HEV RNA positive. The nucleotide sequences of a 304 bp region within HEV ORF2 have identity ranging from 84.5% to 100% among the rabbit isolates and from 82.3% to 100% among the swine isolates. In contrast, the nucleotide identity between the two species groups was only 72–76.6%. Consequently, the two groups were clearly separated in the phylogenetic tree that showed all of the rabbit isolates are closely related to the rabbit HEV reported recently and the swine isolates belong to genotype 4, including subgenotypes 4a, 4c and 4d. The results showed that HEV is highly prevalent in farmed rabbits and pigs in these areas. However, genotype 4 HEV and rabbit HEV are circulating separately in pigs and rabbits in the same area. In conclusion, there was no evidence of cross-species transmission of HEV between pigs and rabbits. The frequency of HEV transmission events between these two animal species is likely low in commercial farms.     

Cross-species infection of hepatitis E virus in a zoo-like location, including birds

Hepatitis E virus (HEV) is a zoonotic pathogen of which several species of animals are considered to be reservoirs. Thirty-eight faecal samples, obtained from 22 species of animals including birds in a wildlife first-aid centre in Eastern China, were tested for HEV RNA. Our survey revealed that in total 28.9% (95% confidence interval 14.5-43.4) of the faecal samples from various mammals and birds were HEV RNA positive. Sequence and phylogenetic analyses of the 11 isolates demonstrated that all sequences clustered in genotype 4 with 96-100% identity to each other. In addition, serum samples from seven animal handlers have shown that five (71.4%) were seropositive. The findings imply that cross-species infection of HEV had probably occurred in this zoo-like location, and moreover, birds can be infected naturally with mammalian HEV.     

戊型肝炎病毒动物宿主及跨种传播的研究进展

戊型肝炎病毒(HEV)是戊型肝炎的病原体,它是一种主要经粪-口途径传播的肝炎病毒.此文主要介绍了HEV动物宿主及其跨种传播的研究进展,为进一步研究HEV的演化和跨种传播方面提供参考.     

戊型病毒性肝炎研究进展

戊型病毒性肝炎（戊肝）是由戊肝病毒（HepatitisE Virus,HEV）引起的急性病毒性肝炎。HEV是一种单链、非包膜的RNA病毒,分为4个基因型,主要通过粪口途径传播,也可以通过输血传播和母婴传播。戊肝主要在发展中国家流行,但欧美等发达国家亦有散发病例。戊肝是一种人畜共患病。酶联免疫吸附实验（ELISA）是目前用于检测血清HEV抗体最常用的方法。HEV RNA检测可证实HEV感染。目前,HEV疫苗的研究主要集中在HEV基因工程疫苗的研制。2012年10月HEV疫苗上市。采用切断传播途径为主的综合性预防措施可控制该病的流行,接种疫苗也是预防戊型肝炎的重要措施。     

Sources of Hepatitis E Virus Genotype 3 in the Netherlands

Non–travel-related hepatitis E virus (HEV) genotype 3 infections in persons in the Netherlands may have a zoonotic, foodborne, or water-borne origin. Possible reservoirs for HEV transmission by water, food, and animals were studied. HEV genotype 3/open reading frame 2 sequences were detected in 53% of pig farms, 4% of wild boar feces, and 17% of surface water samples. HEV sequences grouped within 4 genotype 3 clusters, of which 1 is so far unique to the Netherlands. The 2 largest clusters contained 35% and 43% of the animal and environmental sequences and 75% and 6%, respectively, of human HEV sequences obtained from a study on Dutch hepatitis E patients. This finding suggests that infection risk may be also dependent on transmission routes other than the ones currently studied. Besides the route of exposure, virus characteristics may be an important determinant for HEV disease in humans.     

Development of a vectored vaccine against Hepatitis E virus

Hepatitis E virus is a non-enveloped ssRNA virus [1] that causes human acute hepatitis through primarily fecal and oral transmission [2]. Currently, no commercial hepatitis E (HEV) vaccine is available. In the absence of an appropriate cell culture system for HEV propagation, HEV pseudocapsids (ORF2 protein) have been produced either in Escherichia coli or in insect cells and they have been shown to protect monkeys against virus challenge and to be effective in the prevention of natural HEV infection of humans.