An outbreak of hepatitis E in Northern Namibia, 1983.
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In 1983 in Namibia's Kavango region, epidemic jaundice affected hundreds of people living in settlements lacking potable water and waste disposal facilities. Many were Angolan refugees. The disease, which after investigation was designated non-A non-B hepatitis, was most common in males (72%), in persons aged 15-39 years, and was usually mild except in pregnant women, who incurred 6 (86%) of the 7 fatal infections. Fifteen years later, archived outbreak-associated samples were analyzed. Hepatitis E virus (HEV) was detected by reverse transcription-polymerase chain reaction in feces from 9 of 16 patients tested. Total Ig and IgM to HEV were quantitated in serum from 24 residents of an affected settlement at the outbreak's end: 42% had IgM diagnostic of recent infection and 25% had elevated total Ig without IgM, consistent with past HEV infection. The Namibia outbreak was typical hepatitis E clinically and epidemiologically. This first report of hepatitis E confirmed by virus detection from southern Africa extends the known range of HEV and highlights its risk for refugees. (+info)
Prevalence of enterically transmitted hepatitis viruses in patients attending a tertiary--care hospital in south India.
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The prevalance of enterically transmitted hepatitis viruses, namely, hepatitis A virus (HAV) and hepatitis E virus (HEV) were studied in 404 patients with acute hepatitis attending a tertiary-care hospital in south India. Presence of current HAV/HEV infection was ascertained by the demonstration of IgM antibodies. In 381 patients tested for both agents, HAV IgM was present in 51(13.3%) and HEV IgM present in 66(17.3%). There was dual infection in 3 males (0.8%). HEV infection was seen mostly in older children and adults with only 5.5% occurring in children < 12 years of age. HAV infection was commonly seen to occur in < 12 years of age group (52.7%). One hundred and twenty-six patients were from the Vellore region, among whom HAV and/or HEV aetiology was observed in 28.5%. In this region there did not appear to be any correlation between occurrence of acute hepatitis due to these viruses and rainfall or environmental temperature. Acute hepatitis due to enteric hepatitis viruses was seen throughout the year. (+info)
Virus-specific mRNA capping enzyme encoded by hepatitis E virus.
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Hepatitis E virus (HEV), a positive-strand RNA virus, is an important causative agent of waterborne hepatitis. Expression of cDNA (encoding amino acids 1 to 979 of HEV nonstructural open reading frame 1) in insect cells resulted in synthesis of a 110-kDa protein (P110), a fraction of which was proteolytically processed to an 80-kDa protein. P110 was tightly bound to cytoplasmic membranes, from which it could be released by detergents. Immunopurified P110 catalyzed transfer of a methyl group from S-adenosylmethionine (AdoMet) to GTP and GDP to yield m(7)GTP or m(7)GDP. GMP, GpppG, and GpppA were poor substrates for the P110 methyltransferase. There was no evidence for further methylation of m(7)GTP when it was used as a substrate for the methyltransferase. P110 was also a guanylyltransferase, which formed a covalent complex, P110-m(7)GMP, in the presence of AdoMet and GTP, because radioactivity from both [alpha-(32)P]GTP and [(3)H-methyl]AdoMet was found in the covalent guanylate complex. Since both methyltransferase and guanylyltransferase reactions are strictly virus specific, they should offer optimal targets for development of antiviral drugs. Cap analogs such as m(7)GTP, m(7)GDP, et(2)m(7)GMP, and m(2)et(7)GMP inhibited the methyltransferase reaction. HEV P110 capping enzyme has similar properties to the methyltransferase and guanylyltransferase of alphavirus nsP1, tobacco mosaic virus P126, brome mosaic virus replicase protein 1a, and bamboo mosaic virus (a potexvirus) nonstructural protein, indicating there is a common evolutionary origin of these distantly related plant and animal virus families. (+info)
Acute hepatitis caused by a novel strain of hepatitis E virus most closely related to United States strains.
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A unique hepatitis E virus (HEV) strain was identified as the aetiological agent of acute hepatitis in a United States (US) patient who had recently returned from vacation in Thailand, a country in which HEV is endemic. Sequence comparison showed that this HEV strain was most similar, but not identical, to the swine and human HEV strains recovered in the US. Phylogenetic analysis revealed that this new HEV isolate was closer to genotype 3 strains than to the genotype 1 strains common in Asia. The fact that this HEV was closely related to strains recovered in countries where HEV is not endemic and was highly divergent from Asian HEV strains raises the questions of where the patient's infection was acquired and of whether strains are geographically as localized as once thought. (+info)
Full-genome nucleotide sequence of a hepatitis E virus strain that may be indigenous to Japan.
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We identified hepatitis E virus (HEV) RNA in serum from a Japanese patient with acute hepatitis, who had never been abroad. The full-genome nucleotide sequence of the HEV isolate (JRA1) from this patient was composed of 7227 nucleotides excepting the poly(A) tail and had ORF1 coding for 1703 amino acids (aa), ORF2 coding for 660 aa, and ORF3 coding for 122 aa. This Japanese strain showed approximately 87% nucleotide similarity to human and swine strains reported from the United States, while it had only 73-76% similarity to Asian and Mexican strains. Here we report the characteristics of the HEV-JRA1 isolate, which might be the first example of an indigenous strain(s) of HEV in Japan. (+info)
Evidence of extrahepatic sites of replication of the hepatitis E virus in a swine model.
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Hepatitis E virus (HEV) is the major cause of enterically transmitted non-A, non-B hepatitis in many developing countries and is also endemic in many industrialized countries. Due to the lack of an effective cell culture system and a practical animal model, the mechanisms of HEV pathogenesis and replication are poorly understood. Our recent identification of swine HEV from pigs affords us an opportunity to systematically study HEV replication and pathogenesis in a swine model. In an early study, we experimentally infected specific-pathogen-free pigs with two strains of HEV: swine HEV and the US-2 strain of human HEV. Eighteen pigs (group 1) were inoculated intravenously with swine HEV, 19 pigs (group 2) were inoculated with the US-2 strain of human HEV, and 17 pigs (group 3) were used as uninoculated controls. The clinical and pathological findings have been previously reported. In this expanded study, we aim to identify the potential extrahepatic sites of HEV replication using the swine model. Two pigs from each group were necropsied at 3, 7, 14, 20, 27, and 55 days postinoculation (DPI). Thirteen different types of tissues and organs were collected from each necropsied animal. Reverse transcriptase PCR (RT-PCR) was used to detect the presence of positive-strand HEV RNA in each tissue collected during necropsy at different DPI. A negative-strand-specific RT-PCR was standardized and used to detect the replicative, negative strand of HEV RNA from tissues that tested positive for the positive-strand RNA. As expected, positive-strand HEV RNA was detected in almost every type of tissue at some time point during the viremic period between 3 and 27 DPI. Positive-strand HEV RNA was still detectable in some tissues in the absence of serum HEV RNA from both swine HEV- and human HEV-inoculated pigs. However, replicative, negative-strand HEV RNA was detected primarily in the small intestines, lymph nodes, colons, and livers. Our results indicate that HEV replicates in tissues other than the liver. The data from this study may have important implications for HEV pathogenesis, xenotransplantation, and the development of an in vitro cell culture system for HEV. (+info)
Genetic identification and characterization of a novel virus related to human hepatitis E virus from chickens with hepatitis-splenomegaly syndrome in the United States.
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Hepatitis-splenomegaly (HS) syndrome is an emerging disease in chickens in North America; the cause of this disease is unknown. In this study, the genetic identification and characterization of a novel virus related to human hepatitis E virus (HEV) isolated from bile samples of chickens with HS syndrome is reported. Based upon the similar genomic organization and significant sequence identity of this virus with HEV, the virus has been tentatively named avian HEV in order to distinguish it from human and swine HEV. Electron microscopy revealed that avian HEV is a non-enveloped virus particle of 30-35 nm in diameter. The sequence of the 3' half of the viral genome ( approximately 4 kb) was determined. Sequence analyses revealed that this genomic region contains the complete 3' non-coding region, the complete genes from open reading frames (ORFs) 2 and 3, the complete RNA-dependent RNA polymerase (RdRp) gene and a partial helicase gene from ORF 1. The helicase gene is the most conserved gene between avian HEV and other HEV strains, displaying 58-61% aa and 57-60% nt sequence identities. The RdRp gene of avian HEV shares 47-50% aa and 52-53% nt sequence identities and the putative capsid gene (ORF 2) of avian HEV shares 48-49% aa and 48-51% nt sequence identities with the corresponding regions of other known HEV strains. Phylogenetic analysis indicates that avian HEV is genetically related to, but distinct from, other known HEV strains. This discovery has important implications for HEV animal models, nomenclature and natural history. (+info)
Identification and characterization of the neutralization epitope(s) of the hepatitis E virus.
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The neutralization epitope(s) of the hepatitis E virus (HEV) was studied by an in vitro neutralization assay using antibodies obtained by immunization of mice with 51 overlapping 30-mer synthetic peptides spanning the region 221-660 amino acids (aa) of the HEV open reading frame 2 encoded protein (pORF2) and 31 overlapping recombinant proteins of different sizes derived from the entire pORF2 of the HEV Burma strain. Antibodies against synthetic peptides and short recombinant proteins of approximately 100 aa did not neutralize HEV, suggesting the HEV neutralization epitope(s) is conformation-dependent. However, one recombinant protein of approximately 400 aa in length comprising the pORF2 sequence at position 274-660 aa as well as all truncated derivatives of this protein containing region 452-617 aa elicited antibodies, demonstrating HEV neutralizing activity. These findings establish for the first time that the minimal size fragment, designated pB166, that can efficiently model the neutralization epitope(s) is 166 aa in length and is located at position 452-617 aa of the HEV pORF2. Additionally, antibodies against pB166 were found to cross-neutralize three different HEV genotypes, suggesting that a common neutralization epitope(s) may exist within the different HEV genotypes. Thus, recombinant proteins constructed in this study may be considered as potential candidates for the development of an HEV subunit vaccine as well as for the development of highly sensitive and specific diagnostic tests. (+info)