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At least 19 recordsLinked to original sources
PubMed1999

Etiology of sporadic acute viral hepatitis in Taiwan: the role of hepatitis C virus, hepatitis E virus and GB virus-C/hepatitis G virus in an endemic area of hepatitis A and B.

The etiology of sporadic acute hepatitis was studied in 334 consecutive patients from Taiwan (237 men and 97 women, aged 16-81 years), with emphasis on the role of hepatitis C virus (HCV), hepatitis E virus (HEV), and GB virus-C/hepatitis G virus (GBV-C/HGV) in acute non-A, non-B (NANB) hepatitis and in HBsAg carriers with superimposed acute hepatitis. According to the conventional diagnostic criteria, there were 12 cases (3.6%) of acute hepatitis A, 17 cases (5.1%) of acute hepatitis B, 128 cases (38.3%) of acute NANB hepatitis, and 177 cases (53.0%) of acute hepatitis in HBsAg carriers (those who were HBsAg positive but IgM anti-HBc negative). Among 128 cases of acute NANB hepatitis, 70 (54.7%) had acute hepatitis C (HCV RNA positive), 5 (3.9%) had acute hepatitis E (IgM anti-HEV positive), and the other 53 (41.4%) were presumably acute hepatitis non-A-E. The prevalence of acute hepatitis A, B, E, and non-A-E showed no significant sex difference, whereas acute hepatitis C was significantly more prevalent in females. The prevalence of acute hepatitis A and B decreased and that of acute hepatitis C increased significantly with increasing age. In contrast, acute hepatitis E and non-A-E showed no significant age predominance. Of 177 HBsAg carriers with acute hepatitis, 64 (36.1%) demonstrated non-B hepatotropic virus superinfection, with HCV being the most common (60.9%), followed by hepatitis D, E, and A viruses, and the other 55 (31.1%) and 58 (32.8%) were presumed to have acute exacerbation of chronic hepatitis B or superimposed acute hepatitis non-A-E, respectively. Serum GBV-C/HGV RNA was detected in 3-4% of acute hepatitis non-A-E cases, suggesting its limited role in these cases.

Acute Disease↗
PubMedDate not supplied

Hepatitis E virus.

Hepatitis E virus (HEV) is a positive-stranded RNA virus with a 7.2 kb genome that is capped and polyadenylated. The virus is currently unclassified: the organisation of the genome resembles that of the Caliciviridae but sequence analyses suggest it is more closely related to the Togaviridae. Hepatitis E virus is an enterically transmitted virus that causes both epidemics and sporadic cases of acute hepatitis in many countries of Asia and Africa but only rarely causes disease in more industrialised countries. Initially the virus was believed to have a limited geographical distribution. However, serological studies suggest that HEV may be endemic also in the United States and Europe even though it infrequently causes overt disease in these countries. Many different animal species worldwide recently have been shown to have antibodies to HEV suggesting that hepatitis E may be zoonotic. Although two related strains have been experimentally transmitted between species, direct transmission from an animal to a human has not been documented. There are four currently recognised genotypes and two of the four contain viruses isolated from swine as well as from humans. Regardless of country of origin or genotype of the virus, most, if not all, strains belong to a single serotype. A promising recombinant vaccine candidate comprised of a truncated capsid protein is currently under evaluation in Nepal.

Animals↗
PubMed2004

[Is endemic hepatitis E infection present in developed countries?--Accumulating information about the hepatitis E virus and hepatitis E infection].

There are several new data on the acute viral hepatitis particularly on infectious non-A-non-C hepatitis viruses. The hepatitis E virus infection was originally thought to be limited only for certain geographic areas and humans. Recently, it has been demonstrated the genetic diversity and worldwide distribution of hepatitis E virus in human population, as well as, the circulation of the virus in many species of animals. It is evident, that hepatitis E virus can spread by fecally contaminated water (waterborne transmission), by meat of infected animals (food-borne transmission), by animal-human contact (zoonotic transmission), and even by transfusion (blood-borne transmission). The frequency of hepatitis E virus infections among the acute hepatitis cases with unknown origin is supposed to be more than 10%. In the differential diagnosis of hepatitis, possible hepatitis E virus infection must be now taken into account even in those areas and countries, like in Hungary, where the infection was previously thought to be non-endemic. To confirm the clinical diagnosis of hepatitis E virus infection, virus specific ELISA and molecular methods are now available. In the near future, a molecular epidemiological study will be organized for the detection of hepatitis E virus in Hungary in collaboration with 9 European countries.--This review covers all aspects of the hepatitis E virus infection including the characteristics and transmission of the etiological agent, the clinical symptoms, its epidemiology, laboratory diagnosis, and some possible control measures.

Developed Countries↗
PubMed2001

A review of hepatitis E virus.

Hepatitis E virus (HEV) is a major cause of outbreaks and sporadic cases of viral hepatitis in tropical and subtropical countries but is infrequent in industrialized countries. The virus is transmitted by the fecal-oral route with fecally contaminated drinking water being the usual vehicle. Hepatitis resulting from HEV infection is a moderately severe jaundice that is self-limiting in most patients. Young adults, 15 to 30 years of age, are the main targets of infection, and the overall death rate is 0.5 to 3.0%. However, the death rate during pregnancy approaches 15 to 25%. Death of the mother and fetus, abortion, premature delivery, or death of a live-born baby soon after birth are common complications of hepatitis E infection during pregnancy. Hepatitis E virus is found in both wild and domestic animals; thus, HEV is a zoonotic virus. The viruses isolated from swine in the United States or Taiwan are closely related to human HEV found in those areas. The close genetic relationship of the swine and human virus suggests that swine may be a reservoir of HEV. In areas where swine are raised, swine manure could be a source of HEV contamination of irrigation water or coastal waters with concomitant contamination of produce or shellfish. Increasing globalization of food markets by industrialized countries has the potential of introducing HEV into new areas of the world. The purpose of this review is to cover certain aspects of hepatitis E including the causative agent, the disease, diagnosis, viral detection, viral transmission, epidemiology, populations targeted by HEV, and the role of animals as potential vectors of the virus.

Animals↗
PubMed1999

Molecular biology and pathogenesis of hepatitis E virus.

Hepatitis E virus (HEV) infection results in hepatitis E, an acute and self-limited disease. The virus is transmitted in a faecal-oral manner and is a major cause of viral hepatitis in much of the developing world, where it causes rampant sporadic infections and large epidemics. A curious feature of hepatitis E is the unusually high rates of mortality that are observed in pregnant women, in whom the disease is exacerbated by the development of fulminant liver disease. In the absence of viable in vitro propagation systems, several geographical isolates of HEV have been maintained in vivo in nonhuman primates and, subsequently,the viral genome has been cloned and sequenced. HEV has been classified provisionally into a separate family known as the HEV-like viruses, which has at least four recognised genotypes, but has only a single serotype. The viral genome is a positive-stranded (+)RNA of ~7.5 kb and encodes at least three proteins. Open reading frame 1 ( ORF1) encodes the viral nonstructural polyprotein, which has domains that are homologous to some of the replication and processing enzymes found in other +RNA viruses. The HEV protein itself remains poorly characterised. The protein encoded by open reading frame 2( ORF2) is the major HEV capsid protein, and the protein encoded by open reading frame 3 ( ORF3) appears to be involved in virus-host interactions. Several questions related to the biology, epidemiology and pathogenesis of HEV remain unanswered; the progress of a few of these is reviewed here.

News↗
PubMed2003

Use of heteroduplex mobility assays (HMA) for pre-sequencing screening and identification of variant strains of swine and avian hepatitis E viruses.

Hepatitis E virus (HEV), the causative agent of human hepatitis E, is an important public health problem in many developing countries and is also endemic in many industrialized countries including the US. The discoveries of avian and swine HEVs by our group from chickens and pigs, respectively, suggest that hepatitis E may be a zoonosis. Current methods for molecular epidemiological studies of HEV require PCR amplification of field strains of HEV followed by DNA sequencing and sequence analyses, which are laborious and expensive. As novel or variant strains of HEV continue to evolve rapidly both in humans and other animals, it is important to develop a rapid pre-sequencing screening method to select field isolates for further molecular characterization. In this study, we developed two heteroduplex mobility assays (HMA) (one for swine HEV based on the ORF2 region, and the other for avian HEV based on the ORF1 region) to genetically differentiate field strains of avian and swine HEVs from known reference strains. The ORF2 regions of 22 swine HEV isolates and the ORF1 regions of 13 avian HEV isolates were amplified by PCR, sequenced and analyzed by HMA against reference prototype swine HEV strain and reference prototype avian HEV strain, respectively. We showed that, in general, the HMA profiles correlate well with nucleotide sequence identities and with phylogenetic clustering between field strains and the reference swine HEV or avian HEV strains. Field isolates with similar HMA patterns generally showed similar sequence identities with the reference strains and clustered together in the phylogenetic trees. Therefore, by using different HEV isolates as references, the HMA developed in this study can be used as a pre-sequencing screening tool to identify variant HEV isolates for further molecular epidemiological studies.

Animals↗
PubMed2001

Genetic heterogeneity of hepatitis E virus.

Hepatitis E virus (HEV) infection has been considered a disease associated with developing regions and attributed to oral-fecal transmission due to inadequate sanitation. Several recent findings, however, have led to a new understanding of this virus. A number of novel isolates have been identified in patients with acute hepatitis from regions not considered endemic for HEV, and these individuals reported no recent travel to HEV endemic areas. In addition, a number of HEV-like sequences have also been isolated from swine worldwide, suggesting the potential of an animal reservoir. Although full-length sequence is available for some strains, the majority of HEV isolates have only been sequenced partially. Sequence comparisons and phylogenetic analyses were performed to determine the genotypic distribution of HEV isolates, based on the partial sequence data available. It has been suggested that HEV isolates segregate into four major genotypes based on full-length comparisons. These analyses, however, indicate that HEV may be distributed into at least nine different groups.

Animals↗
PubMedDate not supplied

Hepatitis E virus.

Hepatitis E virus (HEV) is the aetiological agent of non-HAV enterically transmitted hepatitis. It is the major cause of sporadic as well as epidemic hepatitis, which is no longer confined to Asia and developing countries but has also become a concern of the developed nations. In the Indian subcontinent, it accounts for 30-60% of sporadic hepatitis. It is generally accepted that hepatitis E is mostly self-limited and never progresses to chronicity. It has a higher mortality in pregnant women where the disease condition is accentuated with the development of fulminant liver disease. Currently, no antiviral drug or vaccine is licensed for HEV, although a vaccine candidate is in clinical trials. HEV genome is 7.2kb in size with three open reading frames (ORFs) and 5' and 3' cis acting elements, which have important roles to play in HEV replication and transcription. ORF1 codes for methyl transferase, protease, helicase and replicase; ORF2 codes for the capsid protein and ORF3 for a protein of undefined function. HEV has recently been classified in the genus Hepevirus of the family Hepeviridae. There are four major recognised genotypes with a single known serotype. The absence of a reliable in vitro propagation system is an obstacle to deciphering HEV biology. The genome of HEV has been cloned, sequenced and the infectious nature of these replicons has been established. However, questions related to replication, transcription, virus-host interactions and pathogenesis remain to be answered. This comprehensive review summarises the progress made so far in HEV research, and addresses some of the unanswered questions.

Hepatitis E↗
PubMed2005

A broadly reactive one-step real-time RT-PCR assay for rapid and sensitive detection of hepatitis E virus.

Hepatitis E virus (HEV) is transmitted by the fecal-oral route and causes sporadic and epidemic forms of acute hepatitis. Large waterborne HEV epidemics have been documented exclusively in developing countries. At least four major genotypes of HEV have been reported worldwide: genotype 1 (found primarily in Asian countries), genotype 2 (isolated from a single outbreak in Mexico), genotype 3 (identified in swine and humans in the United States and many other countries), and genotype 4 (identified in humans, swine and other animals in Asia). To better detect and quantitate different HEV strains that may be present in clinical and environmental samples, we developed a rapid and sensitive real-time RT-PCR assay for the detection of HEV RNA. Primers and probes for the real-time RT-PCR were selected based on the multiple sequence alignments of 27 sequences of the ORF3 region. Thirteen HEV isolates representing genotypes 1-4 were used to standardize the real-time RT-PCR assay. The TaqMan assay detected as few as four genome equivalent (GE) copies of HEV plasmid DNA and detected as low as 0.12 50% pig infectious dose (PID50) of swine HEV. Different concentrations of swine HEV (120-1.2PID50) spiked into a surface water concentrate were detected in the real-time RT-PCR assay. This is the first reporting of a broadly reactive TaqMan RT-PCR assay for the detection of HEV in clinical and environmental samples.

Animals↗
PubMed1996

Consecutive evaluation of immunoglobulin M and G antibodies against hepatitis E virus.

Hepatitis E virus (HEV) infection is sporadic in the Guangzhou city southern China. However, the evaluation of antibodies to HEV during consecutive time periods after infection has not been reported. We utilized enzyme immunosorbent assay (ELISA) to defect IgM and IgG anti-HEV in consecutive serum specimens from patients with acute hepatitis E and compared that data with detection rates of IgM and IgG anti-HAV in patients with acute hepatitis A. IgM anti-HEV can be detected as early as 4 days after onset of disease symptoms in some patients. The detection rate of IgM anti-HEV is significantly higher in specimens collected within 4 weeks (95%) of onset than in those specimens collected 4 to 18 weeks after onset (67.6%) (P < 0.005). IgM anti-HEV had a similar pattern to IgM anti-HAV and can be used as a marker of acute HEV infection. In contrast with IgG anti-HAV, 56.8% of the specimens did not contain detectable levels of IgG anti-HEV (P < 0.005). One should be cautioned against making a diagnosis of HEV infection solely by the currently available assays for IgG anti-HEV. In conclusion, IgM anti-HEV can be used as a reliable and sensitive marker for recent HEV infection, but serum specimens should be collected within 4 weeks after onset of symptoms to avoid false-negative results. In contrast, we should be aware of the failure to develop IgG anti-HEV in some patients. These patients carry the risk of reinfection.

Acute Disease↗
PubMed1994

[Hepatitis E virus].

Hepatitis E, a faecal-oral waterborne acute viral hepatitis, occurs most frequently in epidemic outbreaks in developing countries. Hepatitis E virus (HEV) is spherical, nonenveloped and varied in size from 27 to 34 nm with a spiked surface. Experimental HEV infection in primates, molecular cloning involving cDNA libraries and recombinant protein technology indicate that the genome can be assigned to a 7.6 kb single stranded positive polyadenylated RNA. In a 5'NS-S poly A 3' molecular structure, three partially overlapping ORF have been identified. Two strains (Burma and Mexico) have been studied and although they related to caliciviruses, the genetic organization indicates that it represents different agents ranged in a new subgroup: the alpha-like viruses. HEV is an important cause of morbidity and mortality in developing countries in the 15 to 40 year age-group and although the mortality rate is low in the general population (0.5 to 3%), it averages 17 to 20% among third-trimester pregnant women. Several sporadic cases have been recently identified among children. The prevalence of anti-HEV antibodies in blood donors ranges from 2 to 3% in North Europe and USA and from 6.8% in Spain to 70% in Thailand. The average incubation period is 6 weeks. Chronic liver disease, persistent viraemia and oncogenicity have not been observed. HEV particles are identified in stool or bile by immune electron microscopy, capture immunoassay or RT-PCR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2006

A bicistronic subgenomic mRNA encodes both the ORF2 and ORF3 proteins of hepatitis E virus.

Hepatitis E virus replicons containing the neomycin resistance gene expressed from open reading frames (ORFs) 2 and 3 were transfected into Huh-7 cells, and stable cell lines containing functional replicons were selected by constant exposure to G418 sulfate. Northern blot analyses detected full-length replicon RNA and a single subgenomic RNA. This subgenomic RNA, which was capped, initiated at nucleotide 5122 downstream of the first two methionine codons in ORF3 and was bicistronic; two closely spaced methionine codons in different reading frames were used for the initiation of ORF3 and ORF2 translation.

Capsid Proteins↗
PubMed2004

Acidic pH enhances structure and structural stability of the capsid protein of hepatitis E virus.

Hepatitis E virus (HEV) is enterically transmitted and endemic to tropical areas of the world. The major capsid protein of HEV is pORF2 ( approximately 74 kDa), encoded by open reading frame 2 (ORF2). When expressed in insect cells, it is processed into a approximately 55 kDa form (n-pORF2). We also generated a mutant, m-pORF2, lacking a C-terminal hydrophobic region shown earlier to be required for its homo-oligomerization. Circular dichroism was used to measure the secondary structure and stability of these proteins as a function of pH and temperature. With decreasing pH both proteins acquired increasing alpha-helicity and thermal stability in terms of midpoint of denaturation and the Gibbs energy change.

Animals↗
PubMed2002

Overview of Hepatitis E Virus.

Hepatitis E virus (HEV) is an enterically transmitted virus usually presenting as an acute self-limiting disease. However, mortality increases dramatically from around 1% to 20% in pregnant women. HEV has been the cause of very large outbreaks of hepatitis in developing countries and is also responsible for a significant number of sporadic cases. It is clear that cases occur outside the endemic areas, and new isolates have been identified. HEV-like viruses have also been found in various animal groups, and it is likely that HEV can be regarded as a zoonotic infection. Preventative measures at the moment depend mainly on the provision of clean water supplies, although a vaccine is now undergoing clinical trials.

Journal Article↗
PubMed1997

Emerging viral pathogens in long-term expatriates (I): Hepatitis E virus.

Hepatitis E virus (HEV) is one of the so-called 'emerging' viral pathogens, whose role is increasingly being recognized. To estimate the risk of HEV infection during long-term stays in HEV-endemic countries, 500 serum samples obtained from development aid workers and their family members who had spent on average 9 years in HEV-endemic regions were tested for antibodies against HEV by ELISA and Immunoblot. We found seroprevalence rates of 5-6% with no significant differences related to gender or area of upbringing (raised in an HEV-endemic vs. nonendemic region). Seroprevalence rates did not increase with increasing number of stays or number of expatriate years. None of 77 children and adolescents tested was positive for anti-HEV. The Indian subcontinent showed the highest seropositive rate with 10%. In subjects returning from West and Central Africa, East Africa, South-east Asia and Latin America seroprevalence rates were around 7%. We found a comparatively low seroprevalence rate of 2.1% for the Arab countries and the Middle East. Our results show that there definitely is a risk for long-term expatriates to acquire HEV infection; however, in most of our cases infection seems to have been non- or oligo-symptomatic.

Adolescent↗
PubMed2001

A yeast two-hybrid study on self-association of the ORF2 protein of hepatitis E virus.

Hepatitis E virus is a human RNA virus containing three open reading frames. Of these, ORF2 encodes the major capsid protein (pORF2) and may possess regulatory functions, in addition to a structural one. In this study, we have shown using the yeast two-hybrid system and in vitro immobilization experiments that full-length pORF2 is capable of self-association, thus forming a homodimer. Using mutational analysis we have studied dimerization of various truncated versions of the ORF2 capsid protein using the yeast two-hybrid system and supported our findings with in vitro immobilization experiments. Deletions of pORF2 reveal a loss of the dimerization potential for all deletions except an N-terminal 127-amino-acid deletion. Our studies suggest that the dimerization property of pORF2 may not be amino-acid sequence dependent but instead a complex formation of a specific tertiary structure that imparts pORF2 its property to self-associate.

Dimerization↗
PubMed1997

Expression and self-assembly of empty virus-like particles of hepatitis E virus.

Hepatitis E virus (HEV) is a pathogenic agent that causes fecally-orally transmitted acute hepatitis. The genome, a single-stranded positive-sense RNA, encodes three forward open reading frames (ORFs), in which an approximately 2-kb structural protein is located in the 3' end. To produce HEV-like particles the structural protein, with its N terminus truncated (amino acid residues 112 to 660 of ORF2), was expressed in insect Tn5 cells by a recombinant baculovirus. In addition to the primary translation product with a molecular mass of 58 kDa, a large amount of a further-processed molecule with a molecular mass of 50 kDa was generated and efficiently released into the culture medium. Electron microscopic observation of the culture medium revealed that the 50-kDa protein self-assembled to form empty virus-like particles (VLPs). The buoyant density of the VLPs in CsCl was 1.285 g/cm3 and their diameter was 23.7 nm, a little smaller than the 27 nm of native HEV particles secreted into the bile or stools of experimentally infected monkeys. The yield of the VLPs was 1 mg per 10(7) cells as a purified form. The particles possess antigenicity similar to that of authentic HEV particles and, consequently, they appear to be a good antigen for the sensitive detection of HEV-specific immunoglobulin G (IgG) and IgM antibodies. Furthermore, the VLP may be the most promising candidate yet for an HEV vaccine, owing to its potent immunogenicity.

Animals↗
PubMed2005

Essential elements of the capsid protein for self-assembly into empty virus-like particles of hepatitis E virus.

Hepatitis E virus (HEV) is a noncultivable virus that causes acute liver failure in humans. The virus's major capsid protein is encoded by an open reading frame 2 (ORF2) gene. When the recombinant protein consisting of amino acid (aa) residues 112 to 660 of ORF2 is expressed with a recombinant baculovirus, the protein self-assembles into virus-like particles (VLPs) (T.-C. Li, Y. Yamakawa, K. Suzuki, M. Tatsumi, M. A. Razak, T. Uchida, N. Takeda, and T. Miyamura, J. Virol. 71:7207-7213, 1997). VLPs can be found in the culture medium of infected Tn5 cells but not in that of Sf9 cells, and the major VLPs have lost the C-terminal 52 aa. To investigate the protein requirement for HEV VLP formation, we prepared 14 baculovirus recombinants to express the capsid proteins truncated at the N terminus, the C terminus, or both. The capsid protein consisting of aa residues 112 to 608 formed VLPs in Sf9 cells, suggesting that particle formation is dependent on the modification process of the ORF2 protein. In the present study, electron cryomicroscopy and image processing of VLPs produced in Sf9 and Tn5 cells indicated that they possess the same configurations and structures. Empty VLPs were found in both Tn5 and Sf9 cells infected with the recombinant containing an N-terminal truncation up to aa residue 125 and C-terminal to aa residue 601, demonstrating that the aa residues 126 to 601 are the essential elements required for the initiation of VLP assembly. The recombinant HEV VLPs are potential mucosal vaccine carrier vehicles for the presentation of foreign antigenic epitopes and may also serve as vectors for the delivery of genes to mucosal tissue for DNA vaccination and gene therapy. The results of the present study provide useful information for constructing recombinant HEV VLPs having novel functions.

Animals↗