Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Viral hepatitis is a common infection in the developing countries. Aside from Hepatitis A-E viruses, a novel hepatitis virus termed GBV-C, or HGV, was recently described. We have studied the prevalence of this virus among Saudi Arabian healthy blood donors (n = 200) and patients with cryptogenic (non-A-E) hepatitis (n=71). After serum extraction and RNA reverse transcription, amplification was carried out by the polymerase chain reaction (PCR), using primers for the 5' noncoding region (NCR), NS5A region and NS3 helicase region. Among the patients with cryptogenic hepatitis, PCR-positivity was 18/71 (25.4%) for the 5' NCR, 14/71 (19.7%) for the NS5A region, and 15/71 (21.1%) for the NS3 helicase region. Among the healthy blood donors, PCR-positivity was 4/200 (2%) for the 5' NCR, 0/200 (0%) for the NS5A region, and 1/200 (0.5%) for the NS3 helicase region. Since the 5' NCR is considered the most conserved segment of the virus genome, it is not unusual to find higher positivity rate when that region is used for amplification. It is noted that the positivity rate is not far different among the three amplified regions, indicating that the heterogeneity of GBV-C/HGV is not as extensive as in hepatitis C virus. Phylogenetic analysis of 5'NCR DNA sequences showed that all isolates in this study belong to genotype 2. We conclude that the prevalence of GBV-C/HGV is similar to what is reported worldwide among the general Saudi population but relatively higher among Saudi patients with cryptogenic hepatitis.
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PMID:GB virus C/hepatitis G virus infection in Saudi Arabian blood donors and patients with cryptogenic hepatitis. 1066 7

Hepatitis E virus (HEV) is an important etiological agent of epidemic and sporadic hepatitis, which is endemic to the Indian subcontinent and prevalent in most of the developing parts of the world. The infection is often associated with acute liver failure and high mortality, particularly in pregnant women. In order to develop methods of intervention, it is essential to understand the biology of the virus. This is particularly important as no reliable in vitro culture system is available. We have constructed a cDNA clone encompassing the complete HEV genome from independently characterized subgenomic fragments of an Indian epidemic isolate. Transfection studies were carried out with HepG2 cells using in vitro-transcribed RNA from this full-length HEV cDNA clone. The presence of negative-sense RNA, indicative of viral replication, was demonstrated in the transfected cells by strand-specific reverse transcription-PCR and slot blot hybridization. The viral proteins pORF2 and pORF3 and processed components of the pORF1 polyprotein (putative methyltransferase, helicase, and RNA-dependent RNA polymerase) were identified in the transfected cells by metabolic pulse-labeling with [(35)S]methionine-cysteine, followed by immunoprecipitation with respective antibodies. The expression of viral proteins in the transfected cells was also demonstrated by immunofluorescence microscopy. Viral replication was detected in the transfected cells up to 33 days posttransfection (six passages). The culture supernatant from the transfected cells was able to produce HEV infection in a rhesus monkey (Macaca mulatta) following intravenous injection, indicating the generation of viable HEV particles following transfection of cells with in vitro-synthesized genomic RNA. This transient cell culture model using in vitro-transcribed RNA should facilitate our understanding of HEV biology.
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PMID:The in vitro-synthesized RNA from a cDNA clone of hepatitis E virus is infectious. 1066 75

To assess the prevalence of GBV-C in patients suffering unknown liver disease we have investigated the GBV-C-RNA in serum of 54 patients: 10 with acute and 32 with chronic non-A-E hepatitis (16 active and 16 persistent), 10 with hepatocellular carcinoma, 2 diagnosed with hepatic fulminant failure, and 91 healthy blood donors (control). PCR with primers from NS3 helicase region was performed and the product was identified by a double strand DNA enzyme immunoassay. GBV appears to infect 40 and 31% of acute or chronic non-A-E hepatitis respectively. Also the GBV genome was found in 1 in 10 samples of hepatocarcinoma, in 2 cases of fulminant hepatitis, and in 1 in 91 of the control group. In spite of these results the role of GBV in the etiology of liver diseases has to be analyzed in more comprehensive studies.
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PMID:GB virus C in patients with liver disease of unknown etiology. 1068 17

The replicase gene (gene 1) of the coronavirus mouse hepatitis virus (MHV) encodes two co-amino-terminal polyproteins presumed to incorporate all the virus-encoded proteins necessary for viral RNA synthesis. The polyproteins are cotranslationally processed by viral proteinases into at least 15 mature proteins, including four predicted cleavage products of less than 25 kDa that together would comprise the final 59 kDa of protein translated from open reading frame 1a. Monospecific antibodies directed against the four distinct domains detected proteins of 10, 12, and 15 kDa (p1a-10, p1a-12, and p1a-15) in MHV-A59-infected DBT cells, in addition to a previously identified 22-kDa protein (p1a-22). When infected cells were probed by immunofluorescence laser confocal microscopy, p1a-10, -22, -12, and -15 were detected in discrete foci that were prominent in the perinuclear region but were widely distributed throughout the cytoplasm as well. Dual-labeling experiments demonstrated colocalization of the majority of p1a-22 in replication complexes with the helicase, nucleocapsid, and 3C-like proteinase, as well as with p1a-10, -12, and -15. p1a-22 was also detected in separate foci adjacent to the replication complexes. The majority of complexes containing the gene 1 proteins were distinct from sites of accumulation of the M assembly protein. However, in perinuclear regions the gene 1 proteins and nucleocapsid were intercalated with sites of M protein localization. These results demonstrate that the complexes known to be involved in RNA synthesis contain multiple gene 1 proteins and are closely associated with structural proteins at presumed sites of virion assembly.
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PMID:Four proteins processed from the replicase gene polyprotein of mouse hepatitis virus colocalize in the cell periphery and adjacent to sites of virion assembly. 1070 55

The coronavirus replicase gene (gene 1) is translated into two co-amino-terminal polyproteins that are proteolytically processed to yield more than 15 mature proteins. Several gene 1 proteins have been shown to localize at sites of viral RNA synthesis in the infected cell cytoplasm, notably on late endosomes at early times of infection. However, both immunofluorescence and electron microscopic studies have also detected gene 1 proteins at sites distinct from the putative sites of viral RNA synthesis or virus assembly. In this study, mouse hepatitis virus (MHV)-infected cells were fractionated and analyzed to determine if gene 1 proteins segregated to more than one membrane population. Following differential centrifugation of lysates of MHV-infected DBT cells, gene 1 proteins as well as the structural N and M proteins were detected almost exclusively in a high-speed small membrane pellet. Following fractionation of the small membrane pellet on an iodixanol density gradient, the gene 1 proteins p28 and helicase cofractionated with dense membranes (1.12 to 1.13 g/ml) that also contained peak concentrations of N. In contrast, p65 and p1a-22 were detected in a distinct population of less dense membranes (1.05 to 1.09 g/ml). Viral RNA was detected in membrane fractions containing helicase, p28, and N but not in the fractions containing p65 and p1a-22. LAMP-1, a marker for late endosomes and lysosomes, was detected in both membrane populations. These results demonstrate that multiple gene 1 proteins segregate into two biochemically distinct but tightly associated membrane populations and that only one of these populations appears to be a site for viral RNA synthesis. The results further suggest that p28 is a component of the viral replication complex whereas the gene 1 proteins p1a-22 and p65 may serve roles during infection that are distinct from viral RNA transcription or replication.
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PMID:Mouse hepatitis virus replicase proteins associate with two distinct populations of intracellular membranes. 1082 72

The coronavirus mouse hepatitis virus (MHV) directs the synthesis of viral RNA on discrete membranous complexes that are distributed throughout the cell cytoplasm. These putative replication complexes are composed of intimately associated but biochemically distinct membrane populations, each of which contains proteins processed from the replicase (gene 1) polyprotein. Specifically, one membrane population contains the gene 1 proteins p65 and p1a-22, while the other contains the gene 1 proteins p28 and helicase, as well as the structural nucleocapsid (N) protein and newly synthesized viral RNA. In this study, immunofluorescence confocal microscopy was used to define the relationship of the membrane populations comprising the putative replication complexes at different times of infection in MHV-A59-infected delayed brain tumor cells. At 5.5 h postinfection (p.i.) the membranes containing N and helicase colocalized with the membranes containing p1a-22/p65 at foci distinct from sites of M accumulation. By 8 to 12 h p.i., however, the membranes containing helicase and N had a predominantly perinuclear distribution and colocalized with M. In contrast, the p1a-22/p65-containing membranes retained a peripheral, punctate distribution at all times of infection and did not colocalize with M. By late times of infection, helicase, N, and M each also colocalized with ERGIC p53, a specific marker for the endoplasmic reticulum-Golgi-intermediate compartment. These data demonstrated that the putative replication complexes separated into component membranes that relocalized during the course of infection. These results suggest that the membrane populations within the MHV replication complex serve distinct functions both in RNA synthesis and in delivery of replication products to sites of virus assembly.
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PMID:Mouse hepatitis virus replicase protein complexes are translocated to sites of M protein accumulation in the ERGIC at late times of infection. 1141 2

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.
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PMID:Genetic identification and characterization of a novel virus related to human hepatitis E virus from chickens with hepatitis-splenomegaly syndrome in the United States. 1156 38

The sequence of the replicase gene of porcine epidemic diarrhoea virus (PEDV) has been determined. This completes the sequence of the entire genome of strain CV777, which was found to be 28,033 nucleotides (nt) in length (excluding the poly A-tail). A cloning strategy, which involves primers based on conserved regions in the predicted ORF1 products from other coronaviruses whose genome sequence has been determined, was used to amplify the equivalent, but as yet unknown, sequence of PEDV. Primary sequences derived from these products were used to design additional primers resulting in the amplification and sequencing of the entire ORF1 of PEDV. Analysis of the nucleotide sequences revealed a small open reading frame (ORF) located near the 5' end (no 99-137), and two large, slightly overlapping ORFs, ORF1a (nt 297-12650) and ORF1b (nt 12605-20641). The ORF1a and ORF1b sequences overlapped at a potential ribosomal frame shift site. The amino acid sequence analysis suggested the presence of several functional motifs within the putative ORF1 protein. By analogy to other coronavirus replicase gene products, three protease and one growth factor-like motif were seen in ORF1a, and one polymerase domain, one metal ion-binding domain, and one helicase motif could be assigned within ORF1b. Comparative amino acid sequence alignments revealed that PEDV is most closely related to human coronavirus (HCoV)-229E and transmissible gastroenteritis virus (TGEV) and less related to murine hepatitis virus (MHV) and infectious bronchitis virus (IBV). These results thus confirm and extend the findings from sequence analysis of the structural genes of PEDV.
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PMID:Completion of the porcine epidemic diarrhoea coronavirus (PEDV) genome sequence. 1172 65

We recently identified and characterized a novel virus, designated avian hepatitis E virus (avian HEV), from chickens with hepatitis-splenomegaly syndrome (HS syndrome) in the United States. Avian HEV is genetically related to but distinct from human and swine HEVs. To determine the extent of genetic variation and the seroprevalence of avian HEV infection in chicken flocks, we genetically identified and characterized 11 additional avian HEV isolates from chickens with HS syndrome and assessed the prevalence of avian HEV antibodies from a total of 1,276 chickens of different ages and breeds from 76 different flocks in five states (California, Colorado, Connecticut, Virginia, and Wisconsin). An enzyme-linked immunosorbent assay using a truncated recombinant avian HEV ORF2 antigen was developed and used to determine avian HEV seroprevalence. About 71% of chicken flocks and 30% of chickens tested in the study were positive for antibodies to avian HEV. About 17% of chickens younger than 18 weeks were seropositive, whereas about 36% of adult chickens were seropositive. By using a reverse transcription-PCR (RT-PCR) assay, we tested 21 bile samples from chickens with HS syndrome in California, Connecticut, New York, and Wisconsin for the presence of avian HEV RNA. Of the 21 bile samples, 12 were positive for 30- to 35-nm HEV-like virus particles by electron microscopy (EM). A total of 11 of the 12 EM-positive bile samples and 6 of the 9 EM-negative bile samples were positive for avian HEV RNA by RT-PCR. The sequences of a 372-bp region within the helicase gene of 11 avian HEV isolates were determined. Sequence analyses revealed that the 11 field isolates of avian HEV had 78 to 100% nucleotide sequence identities to each other, 79 to 88% identities to the prototype avian HEV, 76 to 80% identities to chicken big liver and spleen disease virus, and 56 to 61% identities to other known strains of human and swine HEV. The data from this study indicated that, like swine and human HEVs, avian HEV isolates are genetically heterogenic and that avian HEV infection is enzoonotic in chicken flocks in the United States.
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PMID:Heterogeneity and seroprevalence of a newly identified avian hepatitis e virus from chickens in the United States. 1240 97

Therapy of different manifestations of HCV infection is discussed--after 12 years of the discovery of HCV. In acute hepatitis C the antiviral treatment of the early phase is debated, but if 3 months after the onset the HCV viremia persists, interferon (IFN) therapy may be recommended. Asymptomatic HCV carriers with normal alanine aminotransferase (ALT) do not need antivirals. However, their serum ALT, GGT, gammaglobulin values and liver ultrasound findings should be monitored, to disclose an underlying liver disease, and biopsy is considered, if suspicion of hepatitis raises. In patients with chronic hepatitis C biopsy is mandatory, it may prove mild, moderate or severe histological activity (HAI). Moderate or severe active hepatitis C (> 2 x normal ALT, HAI > 7) should be treated. In the first period of the antiviral treatment for HCV, a standard IFN monotherapy (3 x 3 MU s.c. IFN weekly for 6-12 months) has been used, which resulted in 15-20% sustained response (SR) rate. In the second half of nineties, combination of IFN with an oral nucleoside analogue ribavirin increased the SR to 30-30%, by means of decrease in relapse rate. Recently, pegylated IFN (PEG-IFN) in combination with ribavirin can lead to 60% SR. (Genotype HCV1 patients may show SR of about 40%, HCV 2.3 ones about 80%, respectively). Compensated HCV cirrhosis patients may also be treated with this type of combination, which can possibly inhibit progression. Decompensated cirrhosis needs liver transplantation. In the prevention of HCV infection, screening of blood donors, viral inactivation of blood products, disposable needles and education of risk populations are of basic importance, HCV vaccination, however is not on the horizon yet. Thus, antiviral treatment remains of great significance. Searches for new therapeutic modalities, such as multiple antiviral combinations (e.g amantadin + ribavirin + IFN), protease- and helicase inhibitors, ribozymes and cytokines may result further advances.
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PMID:[Hepatitis C virus infection--after 12 years. Advances in the management of chronic hepatitis C]. 1250 75


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