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Sample records for duck hepatitis virus

  1. Evaluation of anti-hepadnavirus activity of Phyllanthus amarus and Phyllanthus maderaspatensis in duck hepatitis B virus carrier Pekin ducks.

    PubMed

    Munshi, A; Mehrotra, R; Ramesh, R; Panda, S K

    1993-12-01

    Extracts of the two traditional Indian herbs, Phyllanthus amarus (P. amarus) and Phyllanthus maderaspatensis (P. maderaspatensis), described by others as useful in the treatment of chronic hepatitis B virus infection were studied for antiviral properties on duck hepatitis B virus infection. One hundred and fourteen ducks infected posthatch with the duck hepatitis B virus (DHBV) were divided into groups at three months of age and treated intraperitoneally with the aqueous, butanol, and alcoholic extracts of these two plants at doses of 25, 50, or 200 mg/kg body weight. Saline-treated animals served as controls. In the ducks negative for DHBV in serum after treatment, we observed replicative intermediates in the liver. There was no definite antiviral property observed in the treated ducks. PMID:8106861

  2. Proteomic analysis of primary duck hepatocytes infected with duck hepatitis B virus

    PubMed Central

    2010-01-01

    Background Hepatitis B virus (HBV) is a major cause of liver infection in human. Because of the lack of an appropriate cell culture system for supporting HBV infection efficiently, the cellular and molecular mechanisms of hepadnavirus infection remain incompletely understood. Duck heptatitis B virus (DHBV) can naturally infect primary duck hepatocytes (PDHs) that provide valuable model systems for studying hepadnavirus infection in vitro. In this report, we explored global changes in cellular protein expression in DHBV infected PDHs by two-dimension gel electrophoresis (2-DE) combined with MALDI-TOF/TOF tandem mass spectrometry (MS/MS). Results The effects of hepadnavirus infection on hepatocytes were investigated in DHBV infected PDHs by the 2-DE analysis. Proteomic profile of PDHs infected with DHBV were analyzed at 24, 72 and 120 h post-infection by comparing with uninfected PDHs, and 75 differentially expressed protein spots were revealed by 2-DE analysis. Among the selected protein spots, 51 spots were identified corresponding to 42 proteins by MS/MS analysis; most of them were matched to orthologous proteins of Gallus gallus, Anas platyrhynchos or other avian species, including alpha-enolase, lamin A, aconitase 2, cofilin-2 and annexin A2, etc. The down-regulated expression of beta-actin and annexin A2 was confirmed by Western blot analysis, and potential roles of some differentially expressed proteins in the virus-infected cells have been discussed. Conclusions Differentially expressed proteins of DHBV infected PDHs revealed by 2-DE, are involved in carbohydrate metabolism, amino acid metabolism, stress responses and cytoskeleton processes etc, providing the insight to understanding of interactions between hepadnavirus and hepatocytes and molecular mechanisms of hepadnavirus pathogenesis. PMID:20529248

  3. Chemical disinfection of duck hepatitis B virus: a model for inactivation of infectivity of hepatitis B virus.

    PubMed

    Tsiquaye, K N; Barnard, J

    1993-08-01

    The susceptibility of duck hepatitis B virus (DHBV) to the virucidal effects of sodium hypochlorite (NaOCl) and sodium dichloroisocyanurate (NaDCC) was compared to hepatitis B virus (HBV) with the aim of using the duck as a model for studying HBV disinfection. Using viral DNA polymerase (DNAP) as a target, inhibition of DNAP activity by chlorine disinfectants was found to be concentration-dependent but independent of contact time. Two minute exposure of minimal effective concentrations of sodium hypochlorite (domestic bleach: 3600 ppm and industrial bleach: 3180 ppm) and sodium dichloroisocyanurate (3000 ppm available chlorine) to DHBV- and HBV-rich plasma totally inhibited DNA polymerase activity. DHBV particles in DHBV-carrier duck plasma (10(4.5) ID50/mL) were treated with these concentrations and inoculated intravenously into 18 one-day old ducklings (six animals/disinfectant). Analysis of plasma (0, 7 and 14 days post-infection) and post-mortem liver (14 days post-infection) by DNA hybridization techniques showed that DHBV DNA was undetectable in samples from all animals inoculated with disinfected virus particles. However, post-inoculation plasma and liver of 18 of 18 control ducklings inoculated with untreated virions were positive for DHBV DNA. These results show for the first time that total inhibition in vitro of hepadnavirus DNA polymerase activity by chemical disinfectants is predictive of inactivation of infectivity in vivo. PMID:8226434

  4. A comparison of the effects of aflatoxin B1 on the livers of rats and duck hepatitis B virus-infected and noninfected ducks.

    PubMed

    Seawright, A A; Snowden, R T; Olubuyide, I O; Riley, J; Judah, D J; Neal, G E

    1993-07-01

    A need exists for an appropriate animal model for the involvement of both hepatitis B virus infection and ingestion of aflatoxins in the etiology of liver cancer. Duck hepatitis B virus-infected ducks, on the basis of hepatoma development in the wild in China, appear to offer this possibility. The duck has been reexamined as a model system, and key metabolic processes have been assayed in comparison with the rat model for hepatocarcinogenesis. Aflatoxin B1 was found to be more actively metabolized by hepatic microsomes isolated from Pekin ducks in vitro to the aflatoxin B1-8,9-epoxide than corresponding fractions from the rat, and in vivo, higher levels of aflatoxin B1-guanine adduct were formed in hepatic DNA than in the livers of the aflatoxin B1-sensitive F344 rat. Repair of this DNA lesion in the duck and the subsequent formation of the ring-opened aflatoxin B1-FAPy adduct paralleled that in the rat. No effect of duck hepatitis B virus infection was found on any of these biochemical processes. The formation of hepatic lesions was also studied, and lesions were compared with those seen in the aflatoxin B1-treated rat. Histological analysis of necropsy specimens from ducks, 20 mo after the ducks received doses of aflatoxin B1 (25 and 50 micrograms/kg body wt), showed almost complete regression of the early acute lesions, with no evidence of neoplasia. Male F344 rats treated with aflatoxin B1 150 micrograms/kg 5 days/wk for 4 wk had extensive bile duct hyperplasia at the end of the treatment period and 100% incidence of hepatocellular carcinoma after 52 wk. The possible basis for the relative sensitivity of ducks and rats to the carcinogenic action of aflatoxin B1 is discussed. PMID:8325610

  5. Interaction between ganciclovir and foscarnet as inhibitors of duck hepatitis B virus replication in vitro.

    PubMed Central

    Civitico, G; Shaw, T; Locarnini, S

    1996-01-01

    Safe and effective treatments for chronic hepatitis B virus (HBV) infection have yet to be developed. Both ganciclovir (9-[1,3-dihydroxy-2-propoxymethyl]guanine) and foscarnet (trisodium phosphonoformate hexahydrate) are potent inhibitors of hepadnavirus replication when used individually in vitro and in vivo. However, the clinical usefulness of each drug is reduced by dose-limiting toxicity, especially during long-term monotherapy. Here we demonstrate additive inhibition of duck HBV DNA replication in cultures of primary duck hepatocytes congenitally infected with duck HBV by combinations of ganciclovir and foscarnet at low, clinically achievable concentrations. These results suggest that the effects of ganciclovir and foscarnet against HBV may be additive in vivo. PMID:8723462

  6. Inhibition of duck hepatitis B virus replication by mimic peptides in vitro

    PubMed Central

    JIA, HONGYU; LIU, CHANGHONG; YANG, YING; ZHU, HAIHONG; CHEN, FENG; LIU, JIHONG; ZHOU, LINFU

    2015-01-01

    The aim of the present study was to investigate the inhibitory effect of specific mimic peptides targeting duck hepatitis B virus polymerase (DHBVP) on duck hepatitis B virus (DHBV) replication in primary duck hepatocytes. Phage display technology (PDT) was used to screen for mimic peptides specifically targeting DHBVP and the associated coding sequences were determined using DNA sequencing. The selected mimic peptides were then used to treat primary duck hepatocytes infected with DHBV in vitro. Infected hepatocytes expressing the mimic peptides intracellularly were also prepared. The cells were divided into mimic peptide groups (EXP groups), an entecavir-treated group (positive control) and a negative control group. The medium was changed every 48 h. Following a 10-day incubation, the cell supernatants were collected. DHBV-DNA in the cellular nucleus, cytoplasm and culture supernatant was analyzed by quantitative polymerase chain reaction (qPCR). Eight mimic peptides were selected following three PDT screening rounds for investigation in the DHBV-infected primary duck hepatocytes. The qPCR results showed that following direct treatment with mimic peptide 2 or 7, intracellular expression of mimic peptide 2 or 7, or treatment with entecavir, the DHBV-DNA levels in the culture supernatant and cytoplasm of duck hepatocytes were significantly lower than those in the negative control (P<0.05). The cytoplasmic DHBV-DNA content of the cells treated with mimic peptide 7 was lower than that in the other groups (P<0.05). In addition, the DHBV-DNA content of the nuclear fractions following the intracellular expression of mimic peptide 7 was significantly lower than that in the other groups (P<0.05). Mimic peptides specifically targeting DHBVP, administered directly or expressed intracellularly, can significantly inhibit DHBV replication in vitro. PMID:26640539

  7. Production of infectious duck hepatitis B virus in a human hepatoma cell line.

    PubMed Central

    Galle, P R; Schlicht, H J; Fischer, M; Schaller, H

    1988-01-01

    The differentiated human hepatoma cell line Hep-G2 was transfected with cloned duck hepatitis B virus (DHBV) DNA. Introduction of closed circular DNA into the human liver cells resulted in the production of viral proteins: core antigen was detected in the cytoplasm, and e antigen, a related product, was secreted into the medium. Moreover, viral particles were released into the tissue culture medium which were indistinguishable from authentic DHBV by density, antigenicity, DNA polymerase activity, and morphology. Intravenous injection of tissue culture-derived DHBV particles into Pekin ducks established DHBV infection. In conclusion, transfection of human hepatoma cells with cloned DHBV DNA results in the production of infectious virus, as occurs with cloned human hepatitis B virus DNA. Human liver cells are therefore competent to support production of the avian and mammalian hepadnaviruses, indicating that liver-specific viral gene expression is controlled by evolutionarily conserved mechanisms. This new DHBV transfection system offers the opportunity to rapidly produce mutated DHBV which then can be further investigated in Pekin ducks. Images PMID:2833623

  8. Rapid resolution of duck hepatitis B virus infections occurs after massive hepatocellular involvement.

    PubMed Central

    Jilbert, A R; Wu, T T; England, J M; Hall, P M; Carp, N Z; O'Connell, A P; Mason, W S

    1992-01-01

    A study was carried out to determine some of the factors that might distinguish transient from chronic hepadnavirus infection. First, to better characterize chronic infection, Pekin ducks, congenitally infected with the duck hepatitis B virus (DHBV), were used to assess age-dependent variations in viremia, percentage of DHBV-infected hepatocytes, and average levels of DNA replication intermediates in the cytoplasm and of covalently closed circular DNA in the nuclei of infected hepatocytes. Levels of viremia and viral DNA were found to peak at about the time of hatching but persisted at relatively constant levels in chronically infected birds up to 2 years of age. The percentage of infected hepatocytes was also constant, with DHBV replication in virtually 100% of hepatocytes in all birds. Next, we found that adolescent ducks inoculated intravenously with a large dose of DHBV also developed massive infection of hepatocytes with an early but low-level viremia, followed by rapid development of a neutralizing antibody response. No obvious quantitative or qualitative differences between transiently and chronically infected liver tissue were detected in the intracellular markers of viral replication examined. However, in the adolescent duck experiment, DHBV infection was rapidly cleared from the liver even when up to 80% of hepatocytes were initially infected. In all of these ducks, clearance of infection was accompanied by only a mild hepatitis, with no evidence that massive cell death contributed to the clearance. This finding suggested that mechanisms in addition to immune-mediated destruction of hepatocytes might make major contributions to clearance of infections, including physiological turnover of hepatocytes in the presence of a neutralizing antibody response and/or spontaneous loss of the capacity of hepatocytes to support virus replication. Images PMID:1738197

  9. Identification of factor-binding sites in the duck hepatitis B virus enhancer and in vivo effects of enhancer mutations.

    PubMed Central

    Liu, C; Mason, W S; Burch, J B

    1994-01-01

    Hepatitis B viruses (hepadnaviruses) can cause chronic, productive infections of hepatocytes. Analyses of the enhancers and promoters of these viruses in cell lines have suggested a requirement of these elements for liver-enriched transcription factors. In this study, a minimum of seven factor-binding sites on the duck hepatitis B virus enhancer were detected by DNase I footprinting using duck liver nuclear extracts. Among the sites that were tentatively identified were one C/EBP-, one HNF1-, and two HNF3-binding sites. Mutations of the HNF1- and HNF3-like sites, which eliminated factor binding, as assessed by both DNase I footprinting and competitive gel shift assays, were evaluated for their effects on enhancer activity. Using a construct in which human growth hormone was expressed from the viral enhancer and core gene promoter, we found that all of the mutations, either alone or in combination, reduced expression two- to fourfold in LMH chicken hepatoma cells. The mutations in the HNF1 site and one of the HNF3 sites, when inserted into the intact viral genome, also suppressed virus RNA synthesis in primary hepatocyte cultures. Virus carrying the latter HNF3 mutation was also examined for its ability to infect and replicate in ducks. No significant inhibition of virus replication was observed in a short-term assay; however, virus with the HNF3 mutation was apparently unable to grow in the pancreas, a second site of duck hepatitis B virus replication in the duck. Images PMID:8139013

  10. Duck hepatitis B virus covalently closed circular DNA appears to survive hepatocyte mitosis in the growing liver

    SciTech Connect

    Reaiche-Miller, Georget Y.; Thorpe, Michael; Low, Huey Chi; Qiao, Qiao; Scougall, Catherine A.; Mason, William S.; Litwin, Samuel; Jilbert, Allison R.

    2013-11-15

    Nucleos(t)ide analogues that inhibit hepatitis B virus (HBV) DNA replication are typically used as monotherapy for chronically infected patients. Treatment with a nucleos(t)ide analogue eliminates most HBV DNA replication intermediates and produces a gradual decline in levels of covalently closed circular DNA (cccDNA), the template for viral RNA synthesis. It remains uncertain if levels of cccDNA decline primarily through hepatocyte death, or if loss also occurs during hepatocyte mitosis. To determine if cccDNA survives mitosis, growing ducklings infected with duck hepatitis B virus (DHBV) were treated with the nucleoside analogue, Entecavir. Viremia was suppressed at least 10{sup 5}-fold, during a period when average liver mass increased 23-fold. Analysis of the data suggested that if cccDNA synthesis was completely inhibited, at least 49% of cccDNA survived hepatocyte mitosis. However, there was a large duck-to-duck variation in cccDNA levels, suggesting that low level cccDNA synthesis may contribute to this apparent survival through mitosis. - Highlights: • The hepatitis B virus nuclear template is covalently closed circular DNA (cccDNA). • cccDNA was studied during liver growth in duck hepatitis B virus infected ducks. • Virus DNA replication and new cccDNA synthesis were inhibited with Entecavir. • At least 49% of cccDNA appeared to survive hepatocyte mitosis. • Low level virus DNA synthesis may contribute to survival of cccDNA through mitosis.

  11. Entry of Duck Hepatitis B Virus into Primary Duck Liver and Kidney Cells after Discovery of a Fusogenic Region within the Large Surface Protein▿

    PubMed Central

    Maenz, Claudia; Chang, Shau-Feng; Iwanski, Alicja; Bruns, Michael

    2007-01-01

    Hepatitis B viruses exhibit a narrow host range specificity that is believed to be mediated by a domain of the large surface protein, designated L. For duck hepatitis B virus, it has been shown that the pre-S domain of L binds to carboxypeptidase D, a cellular receptor present in many species on a wide variety of cell types. Nonetheless, only hepatocytes become infected. It has remained vague which viral features determine host range specificity and organotropicity. By using chymotrypsin to treat duck hepatitis B virus, we addressed the question of whether a putative fusogenic region within the amino-terminal end of the small surface protein may participate in viral entry and possibly constitute one of the determinants of the host range of the virus. Addition of the enzyme to virions resulted in increased infectivity. Remarkably, even remnants of enzyme-treated subviral particles proved to be inhibitory to infection. A noninfectious deletion mutant devoid of the binding region for carboxypeptidase D could be rendered infectious for primary duck hepatocytes by treatment with chymotrypsin. Although because of the protease treatment mutant and wild-type viruses may have become infectious in an unspecific and receptor-independent manner, their host range specificity was not affected, as shown by the inability of the virus to replicate in different hepatoma cell lines, as well as primary chicken hepatocytes. Instead, the organotropicity of the virus could be reduced, which was demonstrated by infection of primary duck kidney cells. PMID:17360753

  12. Signals for Bidirectional Nucleocytoplasmic Transport in the Duck Hepatitis B Virus Capsid Protein

    PubMed Central

    Mabit, Helene; Breiner, Klaus M.; Knaust, Andreas; Zachmann-Brand, Beate; Schaller, Heinz

    2001-01-01

    Hepadnavirus genome replication involves cytoplasmic and nuclear stages, requiring balanced targeting of cytoplasmic nucleocapsids to the nuclear compartment. In this study, we analyze the signals determining capsid compartmentalization in the duck hepatitis B virus (DHBV) animal model, as this system also allows us to study hepadnavirus infection of cultured primary hepatocytes. Using fusions to the green fluorescent protein as a functional assay, we have identified a nuclear localization signal (NLS) that mediates nuclear pore association of the DHBV nucleocapsid and nuclear import of DHBV core protein (DHBc)-derived polypeptides. The DHBc NLS mapped is unique. It bears homology to repetitive NLS elements previously identified near the carboxy terminus of the capsid protein of hepatitis B virus, the human prototype of the hepadnavirus family, but it maps to a more internal position. In further contrast to the hepatitis B virus core protein NLS, the DHBc NLS is not positioned near phosphorylation target sites that are generally assumed to modulate nucleocytoplasmic transport. In functional assays with a knockout mutant, the DHBc NLS was found to be essential for nuclear pore association of the nucleocapsid. The NLS was found to be also essential for virus production from the full-length DHBV genome in transfected cells and from hepatocytes infected with transcomplemented mutant virus. Finally, the DHBc additionally displayed activity indicative of a nuclear export signal, presumably counterbalancing NLS function in the productive state of the infected cell and thereby preventing nucleoplasmic accumulation of nucleocapsids. PMID:11160696

  13. A novel transcriptional element in circular DNA monomers of the duck hepatitis B virus.

    PubMed

    Beckel-Mitchener, A; Summers, J

    1997-10-01

    We report the presence of two elements, pet and net, that are required for proper transcription of the duck hepatitis B virus (DHBV). These regions were previously identified by using plasmid clones of the virus in transient expression assays (M. Huang and J. Summers, J. Virol. 68:1564-1572, 1994). In this study, we further analyzed these regions by using in vitro-synthesized circular DHBV DNA monomers to mimic the authentic transcriptional template. We observed that pet was required for pregenome transcription from circular viral monomers, and in the absence of pet-dependent transcription, expression of the viral envelope genes was increased. We found that deletion of net in circularized DNA monomers led to the production of abnormally long transcripts due to a failure to form 3' ends during transcription. In addition, we report the presence of a net-like region in the mammalian hepadnavirus woodchuck hepatitis virus. These results are consistent with a model that net is a region involved in transcription termination and that in DHBV, pet is required for transcription complexes to read through this region during the first pass through net. PMID:9311882

  14. DNA Methylation and Regulation of the CD8A after Duck Hepatitis Virus Type 1 Infection

    PubMed Central

    Xu, Qi; Chen, Yang; Zhao, Wen Ming; Huang, Zheng Yang; Zhang, Yang; Li, Xiu; Tong, Yi Yu; Chang, Guo Bing; Duan, Xiu Jun; Chen, Guo Hong

    2014-01-01

    Background Cluster of differentiation 8 (CD8) is expressed in cytotoxic T cells, where it functions as a co-receptor for the T-cell receptor by binding to major histocompatibility complex class I (MHCI) proteins, which present peptides on the cell surface. CD8A is critical for cell-mediated immune defense and T-cell development. CD8A transcription is controlled by several cis-acting elements and trans-acting elements and is also regulated by DNA methylation. However, the epigenetic regulation of CD8A in the duck and its relationship with virus infection are still unclear. Results We investigated the epigenetic transcriptional regulatory mechanisms, such as DNA methylation, for the expression of the CD8A and further evaluated the contribution of such epigenetic regulatory mechanisms to DHV-I infection in the duck. Real-time quantitative polymerase chain reaction (RT-qPCR) revealed the highest level of CD8A expression to be in the thymus, followed by the lungs, spleen, and liver, and the levels of CD8A expression were very low in the kidney, cerebrum, cerebellum, and muscle in the duck. RT-qPCR also demonstrated that the CD8A mRNA was down-regulated significantly in morbid ducklings treated with DHV-1 and up-regulated significantly in non-morbid ducklings in all the tissues tested. In addition, hypermethylation of CD8A was detected in the morbid ducklings, whereas relatively low methylation of CD8A was evident in the non-morbid ducklings. The CD8A mRNA level was negatively associated with the CpG methylation level of CD8A and global methylation status. Conclusions We concluded that the mRNA level of the CD8A was negatively associated with the CpG methylation level of CD8A and global methylation status in the duck, suggesting that the hypermethylation of CD8A may be associated with DHV-1 infection. The first two CpG sites of the CD8A promoter region could be considered as epigenetic biomarkers for resistance breeding against duckling hepatitis disease in the duck

  15. Efficient duck hepatitis B virus production by an avian liver tumor cell line.

    PubMed Central

    Condreay, L D; Aldrich, C E; Coates, L; Mason, W S; Wu, T T

    1990-01-01

    Duck hepatitis B virus (DHBV) is produced in small amounts following transfection of human hepatoma or hepatoblastoma cell lines with cloned viral DNA. In a search for better hosts for DHBV replication, two avian liver cell lines were investigated. One of these cell lines, LMH, produced 5 to 10 times more DNA replicative intermediates and 10 to 20 times more infectious DHBV than did either of the two human cell lines, HuH-7 and Hep G2. Utilization of cell lines in genetic analyses of virus replication is often dependent upon obtaining efficient complementation between cotransfected viral genomes. We assayed transcomplementation of a viral polymerase (pol) gene mutant, which is rather inefficient in transfected human cells, and found that viral DNA synthesis was at least 20 times more efficient following cotransfection of LMH cells than in similarly transfected HuH-7 cells. Recombination, a potential interpretation problem in complementation assays, occurred at low levels in the cotransfected cultures but was substantially reduced or eliminated by creation of an LMH subline stably expressing the viral polymerase. This cell line, pol-7, supported the replication of DHBV pol mutants at ca. 10 to 15% of the level of virus replication obtained following transfection with wild-type viral DNA. By transcomplementation of a pol gene mutant in LMH cells, we were able to produce sufficient virus with the mutant genome to investigate the role of polymerase in covalently closed circular DNA amplification. Our results substantiate the hypothesis that covalently closed circular DNA is synthesized by the viral reverse transcriptase. Images PMID:2352324

  16. Transcriptome Analysis of Duck Liver and Identification of Differentially Expressed Transcripts in Response to Duck Hepatitis A Virus Genotype C Infection

    PubMed Central

    Zhang, Huanrong; Ma, Jing; Yue, Hua

    2013-01-01

    Background Duck is an economically important poultry and animal model for human viral hepatitis B. However, the molecular mechanisms underlying host–virus interaction remain unclear because of limited information on the duck genome. This study aims to characterize the duck normal liver transcriptome and to identify the differentially expressed transcripts at 24 h after duck hepatitis A virus genotype C (DHAV-C) infection using Illumina–Solexa sequencing. Results After removal of low-quality sequences and assembly, a total of 52,757 unigenes was obtained from the normal liver group. Further blast analysis showed that 18,918 unigenes successfully matched the known genes in the database. GO analysis revealed that 25,116 unigenes took part in 61 categories of biological processes, cellular components, and molecular functions. Among the 25 clusters of orthologous group categories (COG), the cluster for “General function prediction only” represented the largest group, followed by “Transcription” and “Replication, recombination, and repair.” KEGG analysis showed that 17,628 unigenes were involved in 301 pathways. Through comparison of normal and infected transcriptome data, we identified 20 significantly differentially expressed unigenes, which were further confirmed by real-time polymerase chain reaction. Of the 20 unigenes, nine matched the known genes in the database, including three up-regulated genes (virus replicase polyprotein, LRRC3B, and PCK1) and six down-regulated genes (CRP, AICL-like 2, L1CAM, CYB26A1, CHAC1, and ADAM32). The remaining 11 novel unigenes that did not match any known genes in the database may provide a basis for the discovery of new transcripts associated with infection. Conclusion This study provided a gene expression pattern for normal duck liver and for the previously unrecognized changes in gene transcription that are altered during DHAV-C infection. Our data revealed useful information for future studies on the duck genome

  17. Merocyanine 540 and Photofrin II as photosensitizers for in vitro killing of duck hepatitis B virus and human hepatoma cells

    NASA Astrophysics Data System (ADS)

    Lin, Tsung-I.; Shien, Yong-Shau; Kao, Ming-Chien

    1994-03-01

    The feasibility of using merocyanine 540 (MC 540) and Photofrin II (PII) as effective photodynamic therapeutic (PDT) agents for killing hepatoma cells and duck hepatitis B virus (DHBV) in vitro was investigated. Cultured duck hepatocytes infected with DHBV and hepatoma cells, Hep 3B and HCC 36, were used as models. MC 540 and PII effectively inhibits the DHBV growth by 90 - 99% in a dose- and light-dependent manner. Photodynamic killing of MC 540 in the two hepatoma cell lines results in 94 - 99% growth inhibition. However, both photosensitizers exhibit dark cytotoxicity (37 - 56%). The present results suggest that MC 540 and PII could be promising and effective photodynamic agents for killing HBV and hepatoma cells.

  18. Assessment of a Flavone-Polysaccharide Based Prescription for Treating Duck Virus Hepatitis

    PubMed Central

    Du, Hongxu; Zhang, Shuaibing; Song, Meiyun; Wang, Yixuan; Zeng, Ling; Chen, Yun; Xiong, Wen; Yang, Jingjing; Yao, Fangke; Wu, Yi; Wang, Deyun; Hu, Yuanliang; Liu, Jiaguo

    2016-01-01

    Because polysaccharide and flavone ingredients display good antiviral activity, we developed a flavone/polysaccharide-containing prescription that would be effective against duck viral hepatitis (DVH) and investigated its hepatoprotective effects. Flavones were derived from Hypericum japonicum (HJF) (entire herb of Hypericum japonicum Thunb) and Salvia plebeia (SPF) (entire herb of Salvia plebeia R. Br.), and polysaccharides were derived from Radix Rehmanniae Recens (RRRP) (dried root of Rehmannia glutinosa Libosch). This prescription combination was based on the theory of syndrome differentiation and treatment in traditional Chinese veterinary medicine. In vitro and in vivo experiments were conducted using the three single ingredients compared to the combined HRS prescription to determine their anti-duck hepatitis A viral (anti-DHAV) activity. The results showed that all experimental conditions displayed anti-DHAV activity, but the HRS prescription presented the best effect. To further investigate the hepatoprotective effect of the HRS prescription on DHAV-induced hepatic injury, we tested the mortality rate, the hepatic pathological severity score, plasma biochemical indexes of hepatic function, blood DHAV gene expression levels and peroxidation damage evaluation indexes and then analyzed correlations among these indexes. The results demonstrated that the HRS prescription significantly decreased the mortality rate, reduced the severity of hepatic injury, decreased the hepatic pathological severity score, depressed blood DHAV gene expression levels, and returned the indexes of hepatic function and peroxidation almost to a normal level. These results indicate that the HRS prescription confers an outstanding hepatoprotective effect, and we expect that it will be developed into a new candidate anti-DHAV drug. PMID:26731101

  19. Tembusu Virus in Ducks, China

    PubMed Central

    Cao, Zhenzhen; Zhang, Cun; Liu, Yuehuan; Ye, Weicheng; Han, Jingwen; Ma, Guoming; Zhang, Dongdong; Xu, Feng; Gao, Xuhui; Tang, Yi; Shi, Shaohua; Wan, Chunhe; Zhang, Chen; He, Bin; Yang, Mengjie; Lu, Xinhao; Huang, Yu; Diao, Youxiang; Ma, Xuejun

    2011-01-01

    In China in 2010, a disease outbreak in egg-laying ducks was associated with a flavivirus. The virus was isolated and partially sequenced. The isolate exhibited 87%–91% identity with strains of Tembusu virus, a mosquito-borne flavivirus of the Ntaya virus group. These findings demonstrate emergence of Tembusu virus in ducks. PMID:22000358

  20. Rapid detection of duck hepatitis A virus genotype C using reverse transcription loop-mediated isothermal amplification.

    PubMed

    Li, Chuanfeng; Chen, Zongyan; Meng, Chunchun; Liu, Guangqing

    2014-02-01

    A one-step reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was used and optimized to develop a rapid and sensitive detection system for duck hepatitis A virus genotype C (DHAV-C) RNA. A set of four specific primers was designed against highly conserved sequences located within the 3D gene from DHAV (strain GX1201). Under optimal reaction conditions, the sensitivity of DHAV-C-specific RT-LAMP was 100-fold higher than that of reverse transcriptase-polymerase chain reaction (RT-PCR), with a detection limit of 0.3pg (6.59×10(4) copies) per reaction. No cross-reactivity was observed from the samples of other duck viruses, which is in good accordance with RT-PCR. Furthermore, a positive reaction can be visually inspected by observing turbidity or color change after the addition of SYBR green I dye. The DHAV-C-specific RT-LAMP assay was applied to the samples and compared with RT-PCR. The positive-sample ratios were 26.7% (12 of 45) by RT-LAMP and 20% (9 of 45) by RT-PCR. Therefore, the newly developed RT-LAMP assay is a rapid, specific, sensitive, and cost-effective method of DHAV-C detection. This assay has potential applications in both clinical diagnosis and field surveillance of DHAV-C infection. PMID:24291148

  1. Enzymatic treatment of duck hepatitis B virus: Topology of the surface proteins for virions and noninfectious subviral particles

    SciTech Connect

    Franke, Claudia; Matschl, Urte; Bruns, Michael . E-mail: mbruns@hpi.uni-hamburg.de

    2007-03-01

    The large surface antigen L of duck hepatitis B virus exhibits a mixed topology with the preS domains of the protein alternatively exposed to the particles' interior or exterior. After separating virions from subviral particles (SVPs), we compared their L topologies and showed that both particle types exhibit the same amount of L with the following differences: 1-preS of intact virions was enzymatically digested with chymotrypsin, whereas in SVPs only half of preS was accessible, 2-phosphorylation of L at S118 was completely removed by phosphatase treatment only in virions, 3-iodine-125 labeling disclosed a higher ratio of exposed preS to S domains in virions compared to SVPs. These data point towards different surface architectures of virions and SVPs. Because the preS domain acts in binding to a cellular receptor of hepatocytes, our findings implicate the exclusion of SVPs as competitors for the receptor binding and entry of virions.

  2. Detection of DNA polymerase activities associated with purified duck hepatitis B virus core particles by using an activity gel assay.

    PubMed Central

    Oberhaus, S M; Newbold, J E

    1993-01-01

    Replication of hepadnaviruses involves reverse transcription of an intermediate RNA molecule. It is generally accepted that this replication scheme is carried out by a virally encoded, multifunctional polymerase which has DNA-dependent DNA polymerase, reverse transcriptase, and RNase H activities. Biochemical studies of the polymerase protein(s) have been limited by the inability to purify useful quantities of functional enzyme from virus particles and, until recently, to express enzymatically active polymerase proteins in heterologous systems. An activity gel assay which detects in situ catalytic activities of DNA polymerases after electrophoresis in partially denaturing polyacrylamide gels was used by M.R. Bavand and O. Laub (J. Virol. 62:626-628, 1988) to show the presence of DNA- and RNA-dependent DNA polymerase activities associated with hepatitis B virus particles produced in vitro. This assay has provided the only means by which hepadnavirus polymerase proteins have been detected in association with enzymatic activities. Since conventional methods have not allowed purification of useful quantities of enzymatically active polymerase protein(s), we have devised a protocol for purifying large quantities of duck hepatitis B virus (DHBV) core particles to near homogeneity. These immature virus particles contain DNA- and RNA-dependent DNA polymerase activities, as shown in the endogenous DNA polymerase assay. We have used the activity gel assay to detect multiple DNA- and RNA-dependent DNA polymerase proteins associated with these purified DHBV core particles. These enzymatically active proteins appear larger than, approximately the same size as, and smaller than an unmodified DHBV polymerase protein predicted from the polymerase open reading frame. This is the first report of the detection of active hepadnavirus core-associated DNA polymerase proteins derived from a natural host. Images PMID:8411359

  3. Circulation and in vivo distribution of duck hepatitis A virus types 1 and 3 in infected ducklings.

    PubMed

    Lin, Shao-Li; Cong, Ri-Chao; Zhang, Rui-Hua; Chen, Jun-Hao; Xia, Lin-Lin; Xie, Zhi-Jing; Wang, Yu; Zhu, Yan-Li; Jiang, Shi-Jin

    2016-02-01

    The circulation of duck hepatitis A virus types 1 (DHAV-1) and 3 (DHAV-3) in Southeast Asia has resulted in a continuously changing epidemiological scenario. In this study, a duplex real-time PCR assay for simultaneous quantitative detection of DHAV-1 and DHAV-3 was established, and 200 liver samples from dead ducklings collected from 31 different flocks in Shandong province, China, were tested. Fifty-eight (29.0 %) samples from 13 flocks were positive for DHAV-1 single infection, 113 (56.5 %) samples from 13 other flocks were positive for DHAV-3 single infection, and 24 samples (12.0 %) from four flocks were positive for both viruses. DHAV-1 and DHAV-3 were detected with high viral loads in all of the organs tested (liver, spleen, pancreas, kidney, heart, thymus, bursa of Fabricius and brain). No significant difference in DHAV-1 and DHAV-3 viral loads was found between singly infected and coinfected samples, and there was no correlation between the viral loads of the two viruses and the age of dead ducklings. To the best of our knowledge, this is the first report about the in vivo distribution of DHAV-1 and DHAV-3 in clinically infected ducklings. PMID:26597185

  4. Duck hepatitis B virus integrations in LMH chicken hepatoma cells: identification and characterization of new episomally derived integrations.

    PubMed Central

    Gong, S S; Jensen, A D; Wang, H; Rogler, C E

    1995-01-01

    While the cytoplasmic phase of the hepadnavirus replication cycle is well understood, very little is known about the nuclear phase. In contrast to retroviruses, proviral integration is not required for hepadnavirus replication; however, some of the viral DNAs in the nucleus are diverted into an integration pathway. Under certain conditions these integrations function as carcinogenic agents. In order to study the integration process, we have utilized LMH-D2 cells, which replicate wild-type duck hepatitis B virus (DHBV), to develop the first protocol to detect and characterize integrations of DHBV originating from episomal viral DNAs. Contrary to expectations, our results showed that stable new integrations are readily detectable in subclones of LMH-D2 cells. Complete characterization of one integration revealed a single-genome-length integrant with the structure of double-stranded linear (DSL) DHBV DNAs which are produced by in situ priming during viral replication. The integration contained a terminal redundancy of 6 bp from the r region of the virus DNA minus strand as well as a direct repeat of 70 bp of cellular DNA. On the basis of the structure of the integrant and the cellular DNA target site, we propose a molecular model for the integration mechanism that has some similarities to that of retroviruses. Identification of DSL hepadnavirus DNA integration suggests the possibility that modified DSL viral DNAs may be the precursors to a class of simple, unrearranged hepadnavirus integrations. PMID:7494330

  5. A one-step duplex rRT-PCR assay for the simultaneous detection of duck hepatitis A virus genotypes 1 and 3.

    PubMed

    Hu, Qin; Zhu, Dekang; Ma, Guangpeng; Cheng, Anchun; Wang, Mingshu; Chen, Shun; Jia, Renyong; Liu, Mafeng; Sun, Kunfeng; Yang, Qiao; Wu, Ying; Chen, Xiaoyue

    2016-10-01

    Duck hepatitis A virus (DHAV) is a highly infectious pathogen that causes significant bleeding lesions in the viscera of ducklings less than 3 weeks old. There are three serotypes of DHAV: serotype 1 (DHAV-1), serotype 2 (DHAV-2) and serotype 3 (DHAV-3). These serotypes have no cross-antigenicity with each other. To establish an rRT-PCR assay for the rapid detection of a mixed infection of DHAV-1 and DHAV-3, two pairs of primers and a pair of matching TaqMan probes were designed based on conserved regions of DHAV-1 VP0 and DHAV-3 VP3. Finally, we established a one-step duplex rRT-PCR assay with high specificity and sensitivity for the simultaneous detection of DHAV-1 and DHAV-3. This method showed no cross-antigenicity with the other pathogens tested, including duck plague virus, Muscovy duck parvovirus, Riemerella anatipestifer, and pathogenic E. coli from ducks. Sensitivity tests identified the minimum detection limits of this method as 98 (DHAV-1) and 10 (DHAV-3) copies/reaction. To validate the method, thirty-eight clinical samples and thirty artificially infected samples collected from dead duck embryos were studied. Thirty-seven samples were positive for DHAV-1, seventeen samples were positive for DHAV-3, and fourteen samples were positive for a mixed infection using the duplex rRT-PCR method. The method established in this study is specific, sensitive, convenient and timesaving and is a powerful tool for detecting DHAV-1, DHAV-3, and their mixed infection and for conducting surveys of pandemic virus strains. PMID:27435338

  6. The carbocyclic analog of 2'-deoxyguanosine induces a prolonged inhibition of duck hepatitis B virus DNA synthesis in primary hepatocyte cultures and in the liver.

    PubMed Central

    Fourel, I; Saputelli, J; Schaffer, P; Mason, W S

    1994-01-01

    The carbocyclic analog of 2'-deoxyguanosine (2'-CDG) is a strong inhibitor of hepatitis B virus (HBV) DNA synthesis in HepG2 cells (P.M. Price, R. Banerjee, and G. Acs, Proc. Natl. Acad. USA 86:8543-8544, 1989). We now report that 2'-CDG inhibited duck hepatitis B virus (DHBV) DNA synthesis in primary cultures of duck hepatocytes and in experimentally infected ducks. Like foscarnet (phosphonoformic acid [PFA]) and 2'-,3'-dideoxycytidine (ddC), 2'-CDG blocked viral DNA replication in primary hepatocyte cultures when present during an infection but failed to inhibit the DNA repair reaction that occurs during the initiation of infection to convert virion relaxed circular DNA to covalently closed circular DNA, the template for viral mRNA transcription. Moreover, as for PFA and ddC, viral RNA synthesis was detected when infection was initiated in the presence 2'-CDG. In another respect, however, 2'-CDG exhibited antiviral activity unlike that of ddC or PFA: a single 1-day treatment of hepatocytes with 2'-CDG blocked initiation of viral DNA synthesis for at least 8 days, irrespective of whether DHBV infection was carried out at the time of drug treatment or several days later. Furthermore, orally administered 2'-CDG was long-acting against DHBV in experimentally infected ducklings. Virus replication was delayed by up to 4 days in ducklings infected after administration of 2'-CDG. These observations of long-lasting efficacy in vitro and in vivo even after oral administration suggest that this inhibitor or a nucleoside with similar pharmacological properties may be ideal for reducing virus replication in patients with chronic HBV infection. Images PMID:8289335

  7. Hepatitis Virus Infections in Poultry.

    PubMed

    Yugo, Danielle M; Hauck, Ruediger; Shivaprasad, H L; Meng, Xiang-Jin

    2016-09-01

    Viral hepatitis in poultry is a complex disease syndrome caused by several viruses belonging to different families including avian hepatitis E virus (HEV), duck hepatitis B virus (DHBV), duck hepatitis A virus (DHAV-1, -2, -3), duck hepatitis virus Types 2 and 3, fowl adenoviruses (FAdV), and turkey hepatitis virus (THV). While these hepatitis viruses share the same target organ, the liver, they each possess unique clinical and biological features. In this article, we aim to review the common and unique features of major poultry hepatitis viruses in an effort to identify the knowledge gaps and aid the prevention and control of poultry viral hepatitis. Avian HEV is an Orthohepevirus B in the family Hepeviridae that naturally infects chickens and consists of three distinct genotypes worldwide. Avian HEV is associated with hepatitis-splenomegaly syndrome or big liver and spleen disease in chickens, although the majority of the infected birds are subclinical. Avihepadnaviruses in the family of Hepadnaviridae have been isolated from ducks, snow geese, white storks, grey herons, cranes, and parrots. DHBV evolved with the host as a noncytopathic form without clinical signs and rarely progressed to chronicity. The outcome for DHBV infection varies by the host's ability to elicit an immune response and is dose and age dependent in ducks, thus mimicking the pathogenesis of human hepatitis B virus (HBV) infections and providing an excellent animal model for human HBV. DHAV is a picornavirus that causes a highly contagious virus infection in ducks with up to 100% flock mortality in ducklings under 6 wk of age, while older birds remain unaffected. The high morbidity and mortality has an economic impact on intensive duck production farming. Duck hepatitis virus Types 2 and 3 are astroviruses in the family of Astroviridae with similarity phylogenetically to turkey astroviruses, implicating the potential for cross-species infections between strains. Duck astrovirus (DAstV) causes

  8. Mortality from duck plague virus in immunosuppressed adult mallard ducks

    SciTech Connect

    Goldberg, D.R.; Yuill, T.M.; Burgess, E.C. )

    1990-07-01

    Environmental contaminants contain chemicals that, if ingested, could affect the immunological status of wild birds, and in particular, their resistance to infectious disease. Immunosuppression caused by environmental contaminants, could have a major impact on waterfowl populations, resulting in increased susceptibility to contagious disease agents. Duck plague virus has caused repeated outbreaks in waterfowl resulting in mortality. In this study, several doses of cyclophosphamide (CY), a known immunosuppressant, were administered to adult mallards (Anas platyrhynchos) to determine if a resultant decrease in resistance to a normally sub-lethal strain of duck plague virus would occur, and induce mortality in these birds. Death occurred in birds given CY only, and in birds given virus and CY, but not in those given virus only. There was significantly greater mortality and more rapid deaths in the duck plague virus-infected groups than in groups receiving only the immunosuppressant. A positively correlated dose-response effect was observed with CY mortalities, irrespective of virus exposure. A fuel oil and a crude oil, common environmental contaminants with immunosuppressive capabilities, were tested to determine if they could produce an effect similar to that of CY. Following 28 days of oral oil administration, the birds were challenged with a sub-lethal dose of duck plague virus. No alteration in resistance to the virus (as measured by mortality) was observed, except in the positive CY control group.

  9. Mortality from duck plague virus in immunosuppressed adult mallard ducks

    USGS Publications Warehouse

    Goldberg, D.R.; Yuill, Thomas M.; Burgess, E.C.

    1990-01-01

    Environmental contaminants contain chemicals that, if ingested, could affect the immunological status of wild birds, and in particular, their resistance to infectious disease. Immunosuppression caused by environmental contaminants, could have a major impact on waterfowl populations, resulting in increased susceptibility to contagious disease agents. Duck plague virus has caused repeated outbreaks in waterfowl resulting in mortality. In this study, several doses of cyclophosphamide (CY), a known immunosuppressant, were administered to adult mallards (Anas platyrhynchos) to determine if a resultant decrease in resistance to a normally sub-lethal strain of duck plague virus would occur, and induce mortality in these birds. Death occurred in birds given CY only, and in birds given virus and CY, but not in those given virus only. There was significantly greater mortality and more rapid deaths in the duck plague virus-infected groups than in groups receiving only the immunosuppressant. A positively correlated dose-response effect was observed with CY mortalities, irrespective of virus exposure. A fuel oil and a crude oil, common environmental contaminants with immunosuppressive capabilities, were tested to determine if they could produce an effect similar to that of CY. Following 28 days of oral oil administration, the birds were challenged with a sub-lethal dose of duck plague virus. No alteration in resistance to the virus (as measured by mortality) was observed, except in the positive CY control group.

  10. Immune responses of ducks infected with duck Tembusu virus

    PubMed Central

    Li, Ning; Wang, Yao; Li, Rong; Liu, Jiyuan; Zhang, Jinzhou; Cai, Yumei; Liu, Sidang; Chai, Tongjie; Wei, Liangmeng

    2015-01-01

    Duck Tembusu virus (DTMUV) can cause serious disease in ducks, characterized by reduced egg production. Although the virus has been isolated and detection methods developed, the host immune responses to DTMUV infection are unclear. Therefore, we systematically examined the expression of immune-related genes and the viral distribution in DTMUV-infected ducks, using quantitative real-time PCR. Our results show that DTMUV replicates quickly in many tissues early in infection, with the highest viral titers in the spleen 1 day after infection. Rig-1, Mda5, and Tlr3 are involved in the host immune response to DTMUV, and the expression of proinflammatory cytokines (Il-1β, –2, –6, Cxcl8) and antiviral proteins (Mx, Oas, etc.) are also upregulated early in infection. The expression of Il-6 increased most significantly in the tissues tested. The upregulation of Mhc-I was observed in the brain and spleen, but the expression of Mhc-II was upregulated in the brain and downregulated in the spleen. The expression of the interferons was also upregulated to different degrees in the spleen but that of the brain was various. Our study suggests that DTMUV replicates rapidly in various tissues and that the host immune responses are activated early in infection. However, the overexpression of cytokines may damage the host. These results extend our understanding of the immune responses of ducks to DTMUV infection, and provide insight into the pathogenesis of DTMUV attributable to host factors. PMID:26005441

  11. cis-Acting sequences in addition to donor and acceptor sites are required for template switching during synthesis of plus-strand DNA for duck hepatitis B virus.

    PubMed Central

    Havert, M B; Loeb, D D

    1997-01-01

    A characteristic of all hepadnaviruses is the relaxed-circular conformation of the DNA genome within an infectious virion. Synthesis of the relaxed-circular genome by reverse transcription requires three template switches. These template switches, as for the template switches or strand transfers of other reverse-transcribing genetic elements, require repeated sequences (the donor and acceptor sites) between which a complementary strand of nucleic acid is transferred. The mechanism for each of the template switches in hepadnaviruses is poorly understood. To determine whether sequences other than the donor and acceptor sites are involved in the template switches of duck hepatitis B virus (DHBV), a series of molecular clones which express viral genomes bearing deletion mutations were analyzed. We found that three regions of the DHBV genome, which are distinct from the donor and acceptor sites, are required for the synthesis of relaxed-circular DNA. One region, located near the 3' end of the minus-strand template, is required for the template switch that circularizes the genome. The other two regions, located in the middle of the genome and near DR2, appear to be required for plus-strand primer translocation. We speculate that these cis-acting sequences may play a role in the organization of the minus-strand DNA template within the capsid particle so that it supports efficient template switching during plus-strand DNA synthesis. PMID:9188603

  12. Efficient strategy for constructing duck enteritis virus-based live attenuated vaccine against homologous and heterologous H5N1 avian influenza virus and duck enteritis virus infection.

    PubMed

    Zou, Zhong; Hu, Yong; Liu, Zhigang; Zhong, Wei; Cao, Hangzhou; Chen, Huanchun; Jin, Meilin

    2015-01-01

    Duck is susceptible to many pathogens, such as duck hepatitis virus, duck enteritis virus (DEV), duck tembusu virus, H5N1 highly pathogenic avian influenza virus (HPAIV) in particular. With the significant role of duck in the evolution of H5N1 HPAIV, control and eradication of H5N1 HPAIV in duck through vaccine immunization is considered an effective method in minimizing the threat of a pandemic outbreak. Consequently, a practical strategy to construct a vaccine against these pathogens should be determined. In this study, the DEV was examined as a candidate vaccine vector to deliver the hemagglutinin (HA) gene of H5N1, and its potential as a polyvalent vaccine was evaluated. A modified mini-F vector was inserted into the gB and UL26 gene junction of the attenuated DEV vaccine strain C-KCE genome to generate an infectious bacterial artificial chromosome (BAC) of C-KCE (vBAC-C-KCE). The HA gene of A/duck/Hubei/xn/2007 (H5N1) was inserted into the C-KCE genome via the mating-assisted genetically integrated cloning (MAGIC) to generate the recombinant vector pBAC-C-KCE-HA. A bivalent vaccine C-KCE-HA was developed by eliminating the BAC backbone. Ducks immunized with C-KCE-HA induced both the cross-reactive antibodies and T cell response against H5. Moreover, C-KCE-HA-immunized ducks provided rapid and long-lasting protection against homologous and heterologous HPAIV H5N1 and DEV clinical signs, death, and primary viral replication. In conclusion, our BAC-C-KCE is a promising platform for developing a polyvalent live attenuated vaccine. PMID:25889564

  13. Identification of duck plague virus by polymerase chain reaction

    USGS Publications Warehouse

    Hansen, W.R.; Brown, Sean E.; Nashold, S.W.; Knudson, D.L.

    1999-01-01

    A polymerase chain reaction (PCR) assay was developed for detecting duck plague virus. A 765-bp EcoRI fragment cloned from the genome of the duck plague vaccine (DP-VAC) virus was sequenced for PCR primer development. The fragment sequence was found by GenBank alignment searches to be similar to the 3a?? ends of an undefined open reading frame and the gene for DNA polymerase protein in other herpesviruses. Three of four primer sets were found to be specific for the DP-VAC virus and 100% (7/7) of field isolates but did not amplify DNA from inclusion body disease of cranes virus. The specificity of one primer set was tested with genome templates from other avian herpesviruses, including those from a golden eagle, bald eagle, great horned owl, snowy owl, peregrine falcon, prairie falcon, pigeon, psittacine, and chicken (infectious laryngotracheitis), but amplicons were not produced. Hence, this PCR test is highly specific for duck plague virus DNA. Two primer sets were able to detect 1 fg of DNA from the duck plague vaccine strain, equivalent to five genome copies. In addition, the ratio of tissue culture infectious doses to genome copies of duck plague vaccine virus from infected duck embryo cells was determined to be 1:100, making the PCR assay 20 times more sensitive than tissue culture for detecting duck plague virus. The speed, sensitivity, and specificity of this PCR provide a greatly improved diagnostic and research tool for studying the epizootiology of duck plague. /// Se desarroll?? una prueba de reacci??n en cadena por la polimerasa para detectar el virus de la peste del pato. Un fragmento EcoRI de 765 pares de bases clonado del genoma del virus vacunal de la peste del pato fue secuenciado para la obtenci??n de los iniciadores de la prueba de la reacci??n en cadena por la polimerasa. En investigaciones de alineaci??n en el banco de genes ('GenBank') se encontr?? que la secuencia del fragmento era similar a los extremos 3a?? de un marco de lectura abierto

  14. [Development and evaluation of an inactivated bivalent vaccine against duck viral hepatitis].

    PubMed

    Yin, Fenggui; Jing, Li; Zhang, Shuang; Yu, Meng; Zhang, Wanlin; Fan, Guobing; Dong, Xiukai; Liu, Wenjun

    2015-11-01

    The rapid mutation and widely spread of duck hepatitis A virus (DHAV) lead to the vast economic loss of the duck industry. To prepare and evaluate bivalent inactivated vaccine laboratory products of DHAV, 6 strains were screened from 201 DHAV-1 strains and 38 DHAV-3 strains by using serotype epidemiological analysis in most of the duck factory. Vaccine candidate strains were selected by ELD50 and LD50 tests in the 6 strains. Continuously passaged, the 5th passaged duck embryos bodies grinding fluid was selected as vaccine virus seeds. The virus seeds were treated with formaldehyde and water in oil in water (W/O/W) emulsions, making into three batches of two bivalent inactivated vaccine laboratory products. The safety test, antibody neutralization test, challenged protection and cross immune protection experiment suggested that the vaccines possessed good safety, and neutralizing antibodies were detected at 7th day and the challenged protection rate reached 90% to 100% at the 14th and 21st day. Moreover, immune duration of ducklings lasted more than five weeks. However, cross-immunity protection experiments with DHAV-SH and DHAV-FS only had 20%-30%. The two bivalent inactivated vaccine laboratory products of duck viral hepatitis were effective and reliable, providing a new method as well as a new product for DHAV prevention and control. PMID:26939441

  15. Effects of petroleum hydrocarbons on hepatic function in the duck

    USGS Publications Warehouse

    Patton, J.F.; Dieter, M.P.

    1980-01-01

    1. The indocyanine green dye clearance test for hepatic function was determined in mallard ducks before and during the chronic ingestion (7 months) of representative paraffinic or aromatic petroleum hydrocarbons (PH). 2. No mortality or visible symptoms of toxicity occured in any of the tests. Ingestion of 4000 ppm aromatic PH produced significant increases in liver (25%), plasma clearance of indocyanine green (33%) and hepatic blood flow (30%). 3. Although the aromatics elicited a greater hepatic stress response than the paraffins, the ducks tolerated high concentrations of PH for extended periods.

  16. Hepatitis B virus (image)

    MedlinePlus

    Hepatitis B is also known as serum hepatitis and is spread through blood and sexual contact. It is ... population. This photograph is an electronmicroscopic image of hepatitis B virus particles. (Image courtesy of the Centers for ...

  17. An outbreak of duck virus enteritis (duck plague) in a captive flock of mixed waterfowl

    USGS Publications Warehouse

    Montgomery, R.D.; Stein, G., Jr.; Novilla, M.N.; Hurley, Sarah S.; Fink, R.J.

    1981-01-01

    An outbreak of duck virus enteritis occurred in a flock of captive waterfowl composed of mallards (Anas platyrhynchos), black ducks (Anas rubripes), and Canada geese (Branta canadensis). Although all three species were housed together, morbidity and mortality were confined to the 227 black ducks and Canada geese, of which 180 died and the rest were left in a weakened condition. Lesions are given for 20 black ducks and 4 Canada geese dying from DVE. In addition, both horizontal and vertical transmission are discussed as possible sources of the virus that caused this outbreak.

  18. Interaction between duck hepatitis B virus and a 170-kilodalton cellular protein is mediated through a neutralizing epitope of the pre-S region and occurs during viral infection.

    PubMed Central

    Tong, S; Li, J; Wands, J R

    1995-01-01

    Identification of cell surface viral binding proteins is important for understanding viral attachment and internalization. We have fused the pre-S domain of the duck hepatitis B virus (DHBV) large envelope protein to glutathione S-transferase and demonstrated a 170-kDa binding protein (p170) in [35S]methionine-labeled duck hepatocyte lysates. This glycoprotein was found abundantly in all extrahepatic tissues infectible with DHBV and in some noninfectible tissues, though it is not secreted into the blood. The interaction of pre-S fusion protein with p170 was competitively inhibited by wild-type DHBV in a dose-dependent manner. In addition, infection of hepatocytes with DHBV blocked the binding of pre-S fusion protein to p170, which suggests a biological role for p170 during natural infection. The p170 binding site was mapped to a conserved sequence of 16 amino acid residues (positions 87 to 102) by using 24 pre-S deletion mutants; this binding domain coincides with a major virus-neutralizing antibody epitope. Furthermore, site-directed mutagenesis revealed that an arginine residue at position 97 is critical for p170 binding. p170 was purified by a combination of ion-exchange and affinity chromatographies, and four peptide sequences were obtained. Two peptides showed significant similarities to human and animal carboxypeptides H, M, and N. Taken together, these results raise the possibility that the p170 binding protein is important during the replication cycle of DHBV. PMID:7474130

  19. Efficacy Evaluation of an Inactivated Duck Tembusu Virus Vaccine.

    PubMed

    Lin, Jian; Liu, Yuehuan; Wang, Xiuqing; Yang, Baoshou; He, Pingyou; Yang, Zhiyuan; Duan, Huijuan; Xie, Jia; Zou, Lihong; Zhao, Jicheng; Pan, Jie

    2015-06-01

    To evaluate the potential use of an inactivated virus-based vaccine for the control and prevention of the newly emerged duck Tembusu virus infection in China, a duck Tembusu virus isolate, Tembusu-HB, was propagated in 12-day-old duck embryos and inactivated by treatment with formaldehyde. The inactivated viral antigen was emulsified with mineral oil, and five batches of the vaccine were manufactured. The immunogenicity and protection efficacy of the vaccine were evaluated in Beijing ducks and Beijing white geese. Results showed that more than 80% of immunized ducks were protected against virulent virus challenge after two intramuscular or subcutaneous injections of the inactivated vaccine, as evidenced by the negative virus isolation results. The protection is also correlated with a positive virus-specific antibody response as detected by ELISA. In contrast, none of the control ducks and geese had any detectable antibody response. Virus was isolated from all control ducks and geese after virulent virus challenge. Interestingly, a variable level of protection (20%-80%) was observed in Beijing white geese immunized twice with the same batches of vaccine, suggesting a species-specific effect of the vaccine. Overall, the results clearly suggest that the inactivated duck Tembusu virus vaccine is immunogenic and provides protection against virulent virus challenge. PMID:26473674

  20. Effect of age on the pathogenesis of duck tembusu virus in Cherry Valley ducks

    PubMed Central

    Li, Ning; Lv, Chuanwei; Yue, Ruichao; Shi, Ying; Wei, Liangmeng; Chai, Tongjie; Liu, Sidang

    2015-01-01

    The effect of host age on the outcome of duck tembusu virus (DTMUV) infection was studied in ducks. Three groups of Cherry Valley ducks at 1, 3, and 7 weeks of age were intramuscularly infected with DTMUV to systematically observe the clinical symptoms, pathological changes, tissue viral loads, and immune responses. Severe clinical symptoms and neurological dysfunction were observed in 1-week-old ducks as early as 2 days post infection (dpi) and some died at 5–7 dpi. Three weeks-old ducks showed similar but milder symptoms and no deaths. However, 7-weeks-old ducks showed only transient loss of appetite. Gross lesions gradually reduced in severity as ducks matured. One-week-old ducks showed endocardial hemorrhage, splenomegaly, swelling in the lymph follicles of the ileum, liver, and kidney swelling with degeneration, and meningeal hyperemia. Three-weeks-old ducks showed only mild pathological lesions. No visible lesions were observed in 7-weeks-old ducks. However, pathological histology analysis demonstrated all infected ducks displayed viral encephalitis. DTMUV could be detected in the brains of 1-week-old ducks as early as 1 dpi and virus titers of most organs in 1-week-old ducks were significantly higher than that of 3- and 7-weeks-old ducks at 3–5 dpi. The patterns of IFN-γ, IL-2, and serum neutralizing antibodies were similar, and there were significant difference between the youngest ducks and the older ducks at early infection stage (P < 0.05). More important is that although the antibody titers of all infected ducks were similar from 9 to 17 dpi, reduced clearance of virus was observed in the youngest groups comparing with the other two groups, indicating that immune system maturity was more important than the presence of neutralizing antibody. In summary, this study demonstrates that viral pathogenesis is strongest in 1-week-old ducks and the age-related immune response plays an important role in the pathogenesis of DTMUV in ducks. PMID:26106382

  1. A survey of North American migratory waterfowl for duck plague (duck virus enteritis) virus

    USGS Publications Warehouse

    Brand, Christopher J.; Docherty, Douglas E.

    1984-01-01

    A survey of migratory waterfowl for duck plague (DP) virus was conducted in the Mississippi and Central flyways during 1982 and in the Atlantic and Pacific flyways during 1983. Cloacal and pharyngeal swabs were collected from 3,169 migratory waterfowl in these four flyways, principally mallards (Anas platyrhynchos L.), black ducks (Anas rubripes Brewster), and pintails (Anas acuta L). In addition 1,033 birds were sampled from areas of recurrent DP outbreaks among nonmigratory and captive waterfowl, and 590 from Lake Andes National Wildlife Refuge, the site of the only known major DP outbreak in migratory waterfowl. Duck plague virus was not found in any of the samples. Results support the hypothesis that DP is not established in North American migratory waterfowl as an enzootic disease.

  2. Experimental infection of duck origin virulent Newcastle disease virus strain in ducks

    PubMed Central

    2014-01-01

    Background Newcastle disease (ND) caused by virulent Newcastle disease virus (NDV) is an acute, highly contagious and fatal viral disease affecting most species of birds. Ducks are generally considered to be natural reservoirs or carriers of NDV while being resistant to NDV strains, even those most virulent for chickens; however, natural ND cases in ducks have been gradually increasing in recent years. In the present study, ducks of different breeds and ages were experimentally infected with duck origin virulent NDV strain duck/Jiangsu/JSD0812/2008 (JSD0812) by various routes to investigate the pathogenicity of NDV in ducks. Results Six breeds (mallard, Gaoyou, Shaoxing, Jinding, Shanma, and Pekin ducks) were infected intramuscularly (IM) with JSD0812 strain at the dose of 5 × 108 ELD50. Susceptibility to NDV infection among breeds varied, per morbidity and mortality. Mallard ducks were the most susceptible, and Pekin ducks the most resistant. Fifteen-, 30-, 45-, 60-, and 110-day-old Gaoyou ducks were infected with JSD0812 strain at the dose of 5 × 108 ELD50 either IM or intranasally (IN) and intraocularly (IO), and their disease development, viral shedding, and virus tissue distribution were determined. The susceptibility of ducks to NDV infection decreased with age. Most deaths occurred in 15- and 30-day-old ducklings infected IM. Ducks infected IN and IO sometimes exhibited clinical signs, but seldom died. Clinical signs were primarily neurologic. Infected ducks could excrete infectious virus from the pharynx and/or cloaca for a short period, which varied with bird age or inoculation route; the longest period was about 7 days. The rate of virus isolation in tissues from infected ducks was generally low, even in those from dead birds, and it appeared to be unrelated to bird age and infection route. Conclusions The results confirmed that some of the naturally occurring NDV virulent strains can cause the disease in ducks, and that ducks play an important

  3. Efficient Strategy to Generate a Vectored Duck Enteritis Virus Delivering Envelope of Duck Tembusu Virus

    PubMed Central

    Zou, Zhong; Liu, Zhigang; Jin, Meilin

    2014-01-01

    Duck Tembusu virus (DTMUV) is a recently emerging pathogenic flavivirus that has resulted in a huge economic loss in the duck industry. However, no vaccine is currently available to control this pathogen. Consequently, a practical strategy to construct a vaccine against this pathogen should be determined. In this study, duck enteritis virus (DEV) was examined as a candidate vaccine vector to deliver the envelope (E) of DTMUV. A modified mini-F vector was inserted into the SORF3 and US2 gene junctions of the attenuated DEV vaccine strain C-KCE genome to generate an infectious bacterial artificial chromosome (BAC) of C-KCE (vBAC-C-KCE). The envelope (E) gene of DTMUV was inserted into the C-KCE genome through the mating-assisted genetically integrated cloning (MAGIC) strategy, resulting in the recombinant vector, pBAC-C-KCE-E. A bivalent vaccine C-KCE-E was generated by eliminating the BAC backbone. Immunofluorescence and western blot analysis results indicated that the E proteins were vigorously expressed in C-KCE-E-infected chicken embryo fibroblasts (CEFs). Duck experiments demonstrated that the insertion of the E gene did not alter the protective efficacy of C-KCE. Moreover, C-KCE-E-immunized ducks induced neutralization antibodies against DTMUV. These results demonstrated, for the first time, that recombinant C-KCE-E can serve as a potential bivalent vaccine against DEV and DTMUV. PMID:24956180

  4. Complete Genome Sequence of Duck Tembusu Virus Isolated from Pekin Ducks in Shanghai, China

    PubMed Central

    Cheng, Yuqiang; Zhang, Chuanpeng; Wang, Hengan; Yan, Yaxian; Ding, Chan

    2015-01-01

    We report here the complete genomic sequence of the duck Tembusu virus (DTMUV) SH001 strain, isolated from Pekin ducks in Shanghai, China, in 2013. The genome of SH001 is 10,990 nucleotides (nt) in length and contains a single open reading frame encoding a putative polyprotein of 3,425 amino acids. PMID:25908131

  5. Hepatitis D Virus Replication.

    PubMed

    Taylor, John M

    2015-11-01

    This work reviews specific related aspects of hepatitis delta virus (HDV) reproduction, including virion structure, the RNA genome, the mode of genome replication, the delta antigens, and the assembly of HDV using the envelope proteins of its helper virus, hepatitis B virus (HBV). These topics are considered with perspectives ranging from a history of discovery through to still-unsolved problems. HDV evolution, virus entry, and associated pathogenic potential and treatment of infections are considered in other articles in this collection. PMID:26525452

  6. The Sequential Tissue Distribution of Duck Tembusu Virus in Adult Ducks

    PubMed Central

    Wu, Li; Liu, Jinxiong; Chen, Pucheng; Jiang, Yongping; Ding, Leilei; Lin, Yuan; Li, Qimeng; He, Xijun; Chen, Qiusheng; Chen, Hualan

    2014-01-01

    In 2010, a novel Tembusu virus (TMUV) that caused a severe decrease in the egg production of ducks was isolated in southeast China. Given the novelty of this duck pathogen, little information is available regarding its pathogenesis. Here, we systematically investigated the replication kinetics of TMUV PTD2010 in adult male and female ducks. We found that PTD2010 was detectable in most of the parenchymatous organs as well as the oviduct and intestinal tract from days 1 to 7 after inoculation. Viral titers were maintained at high levels for at least 9 days in the spleen, kidney, bursa of Fabricius, brain, and ovary. No virus was detected in any of these organs or tissues at 18 days after inoculation. PTD2010, thus, causes systemic infections in male and female ducks; its replication kinetics show similar patterns in most organs, with the exception of the ovaries and testes. PMID:25215289

  7. Post-epizootic surveys of waterfowl for duck plague (duck virus enteritis)

    USGS Publications Warehouse

    Brand, C.J.; Docherty, D.E.

    1988-01-01

    Surviving birds from nine duck plague outbreaks in urban and confined waterfowl were sampled for duck plague (DP) virus and DP antibody during 1979-86. Duck plague virus was found in combined oral and cloacal swabs of birds from three outbreaks, and DP-neutralizing antibody was demonstrated in some birds from all nine outbreaks. Greater prevalence of DP antibody and higher titers were found in survivors from confined populations than from free-flying urban populations. Free-flying waterfowl from within 52 km of four DP outbreak sites were also sampled; virus was not found in any birds, but DP antibody was found in urban waterfowl in the vicinity of an outbreak in Potterville, Michigan. No evidence of exposure to or shedding of DP virus in migratory waterfowl was found in two regions where DP appears enzootic in urban and confined waterfowl (Eastern Shore of Maryland and the vicinity of Sacramento, California).

  8. Pathogenicity of duck plague and innate immune responses of the Cherry Valley ducks to duck plague virus

    PubMed Central

    Li, Ning; Hong, Tianqi; Li, Rong; Guo, Mengjiao; Wang, Yao; Zhang, Jinzhou; Liu, Jiyuan; Cai, Yumei; Liu, Sidang; Chai, Tongjie; Wei, Liangmeng

    2016-01-01

    Duck plague caused by duck plague virus (DPV) is an acute and contagious disease. To better understand the pathogenic mechanism of duck plague virus in ducklings, an infection experiment was performed. Our results showed that typical symptoms were observed in the infected ducklings. DPV could replicate quickly in many tissues, leading to pathological lesions, especially on the spleen. Real-time quantitative PCR demonstrated that expression of many innate immune-related genes was mostly up-regulated in the brain, and the antiviral innate immune response was established, but not sufficient to restrict viral replication. In contrast, although the expression of many major pattern recognition receptors (PRRs) increased in the spleen, the expression of most cytokines was declined. Our study indicates that DPV is a pantropic virus that can replicate rapidly in tissues, causing serious pathological lesions but the immune responses are different in the spleen and brain. To our knowledge, this is the first report to systematically explore the expression profiles of the immune genes in the DPV-infected ducks. Our data provide a foundation for further study of the pathogenicity of duck plague. PMID:27553496

  9. Pathogenicity of duck plague and innate immune responses of the Cherry Valley ducks to duck plague virus.

    PubMed

    Li, Ning; Hong, Tianqi; Li, Rong; Guo, Mengjiao; Wang, Yao; Zhang, Jinzhou; Liu, Jiyuan; Cai, Yumei; Liu, Sidang; Chai, Tongjie; Wei, Liangmeng

    2016-01-01

    Duck plague caused by duck plague virus (DPV) is an acute and contagious disease. To better understand the pathogenic mechanism of duck plague virus in ducklings, an infection experiment was performed. Our results showed that typical symptoms were observed in the infected ducklings. DPV could replicate quickly in many tissues, leading to pathological lesions, especially on the spleen. Real-time quantitative PCR demonstrated that expression of many innate immune-related genes was mostly up-regulated in the brain, and the antiviral innate immune response was established, but not sufficient to restrict viral replication. In contrast, although the expression of many major pattern recognition receptors (PRRs) increased in the spleen, the expression of most cytokines was declined. Our study indicates that DPV is a pantropic virus that can replicate rapidly in tissues, causing serious pathological lesions but the immune responses are different in the spleen and brain. To our knowledge, this is the first report to systematically explore the expression profiles of the immune genes in the DPV-infected ducks. Our data provide a foundation for further study of the pathogenicity of duck plague. PMID:27553496

  10. 2',3'-dideoxy-beta-L-5-fluorocytidine inhibits duck hepatitis B virus reverse transcription and suppresses viral DNA synthesis in hepatocytes, both in vitro and in vivo.

    PubMed Central

    Zoulim, F; Dannaoui, E; Borel, C; Hantz, O; Lin, T S; Liu, S H; Trépo, C; Cheng, Y C

    1996-01-01

    beta-L-Nucleoside analogs represent a new class of potent antiviral agents with low cytotoxicity which provide new hope in the therapy of chronic hepatitis B virus (HBV) infections. We evaluated the anti-HBV activity of 2',3'-dideoxy-beta-L-5-fluorocytidine (beta-L-F-ddC), a beta-L-nucleoside analog derived from 2',3'-dideoxycytidine (ddC), in the duck HBV (DHBV) model. This compound was previously shown to inhibit HBV DNA synthesis in a stably transfected hepatoma cell line (F2215). Using a cell-free system for the expression of an enzymatically active DHBV polymerase, we could demonstrate that the triphosphate form of beta-L-F-ddC does inhibit hepadnavirus reverse transcription. In primary duck hepatocyte culture, beta-L-F-ddC showed a potent inhibitory effect on DHBV DNA synthesis which was concentration dependent. Although beta-L-F-ddC was shown to be less active than ddC against the DHBV reverse transcriptase in vitro, beta-L-F-ddC was a stronger inhibitor in hepatocytes. The oral administration of beta-L-F-ddC in experimentally infected ducklings showed that beta-L-F-ddC is a potent inhibitor of viral replication in vivo. Short-term therapy could not prevent a rebound of viral replication after the drug was withdrawn. Preventive therapy with beta-L-F-ddC could delay the onset of viremia by only 1 day compared with the time to the onset of viremia in the control group. The in vivo inhibitory effect of beta-L-F-ddC was much stronger than that of ddC and was not associated with signs of toxicity. Our data show that beta-L-F-ddC inhibits hepadnavirus reverse transcription and is a strong inhibitor of viral replication both in vitro and in vivo. PMID:8834896

  11. Propagation of viruses infecting waterfowl on continuous cell lines of Muscovy duck (Cairina moschata) origin.

    PubMed

    Mészáros, István; Tóth, Renáta; Bálint, Adám; Dán, Adám; Jordan, Ingo; Zádori, Zoltán

    2014-01-01

    Duck circovirus, duck hepatitis A virus 1, goose parvovirus and goose haemorrhagic polyomavirus are economically damaging pathogens of waterfowl, and replicate poorly or not at all in established cell lines. AGE1.CR, AGE1.CR.pIX and AGE1.CS cell lines, originating from the Muscovy duck, were tested for their suitability to isolate and identify these viruses. Immunofluorescence (IF) and quantitative polymerase chain reaction investigations verified that all cell lines are permissive for all four viruses; however, AGE1.CR.pIX proved to be the most productive and most sensitive for viral infection. IF experiments revealed that the time of one infectious cycle is approximately 12 to 14 h in the AGE1.CR.pIX cells in the case of the three DNA viruses, while it is 10 to 12 h for DHAV-1. Specific viral infectivity and the limit of detection by IF varied between 55 and 1484 copies, depending on the viruses and cell lines. Despite the high sensitivity of the cell lines for viruses, their viral productivity remained relatively low for the investigated field isolates. However, optimization of virus infection and/or the adaptation of the viruses to the cells can raise viral productivity and can make these cell lines suitable for vaccine development and production. PMID:24992264

  12. Development of a stabilizer for lyophilization of an attenuated duck viral hepatitis vaccine.

    PubMed

    Kang, M S; Jang, H; Kim, M C; Kim, M J; Joh, S J; Kwon, J H; Kwon, Y K

    2010-06-01

    The live attenuated vaccine against duck viral hepatitis currently available in Korea requires special freezers for storage and transportation with extra costs involved. The development of a lyophilization stabilizer for live attenuated duck viral hepatitis virus (DHV) vaccines, therefore, has been highly recommended for the wider application of the vaccines. Four conventional vaccine stabilizer formulations containing a disaccharide, such as lactose, trehalose, or sucrose, and new formulations containing sorbitol were tested for their efficacy in stabilizing a new attenuated DHV type 3 vaccine candidate under different storage temperatures, 4 and 37 degrees C. The vaccine virus and each stabilizer formulation were combined and submitted to lyophilization and the viability of the virus was measured in 7-d-old specific-pathogen-free chicken embryos by determining the 50% egg lethal dose. Stabilizer formulations containing 2, 4, or 8% sorbitol preserved the viability of the vaccine virus much better than the other stabilizer formulations and 2% sorbitol was the optimal concentration in a standard stabilizing buffer, phosphate glutamate gelatin (0.0038 M KH2PO4, 0.0071 M K2HPO4, 0.0049 M monosodium L-glutamate, and 0.5% gelatin). The results demonstrate that the stabilizer formulation containing 2% sorbitol and 0.5% gelatin can be used for convenient storage and transportation of live DHV vaccines. PMID:20460663

  13. Liposomes containing recombinant E protein vaccine against duck Tembusu virus in ducks.

    PubMed

    Ma, Tengfei; Liu, Yongxia; Cheng, Jia; Liu, Yanhan; Fan, Wentao; Cheng, Ziqiang; Niu, Xudong; Liu, Jianzhu

    2016-04-27

    To obtain an effective vaccine candidate against duck Tembusu viral (DTMUV) disease which causes egg-drop and great economical loss in the Chinese duck industry, liposome vaccines containing recombinant E protein were prepared and assessed in this study. The recombinant plasmid (PET28a-E) was constructed and transformed into BL21 (DE3) cells to produce E proteins. The recombinant E proteins were purified and entrapped by liposomes through reverse-phase evaporation. Eighty-four cherry valley ducks were randomly divided into seven groups and inoculated intramuscularly at one- or seven-day-old with liposomes-E protein or Freund's adjuvant-E protein vaccine. Blood samples were collected from the first week to the tenth week for serum antibody, plasma for viremia, as well as oropharyngeal and cloacal swabs for virus shedding analyses after being challenged with a 10(2.4) 50% tissue culture infective dose (TCID50) of duck Tembusu virus. Results showed that serum antibody level of the liposomes vaccine was higher than the Freund's adjuvant vaccine, and inoculating twice was superior to once; furthermore, the viremia and virus shedding tests also proved that the liposomes vaccine can provide complete protection against DTMUV challenge. These results demonstrated that the liposomes-E protein vaccine could be used as a potential candidate vaccine to prevent DTMUV infection in ducks. PMID:27016654

  14. Pathogenicity of two Egyptian H5N1 highly pathogenic avian influenza viruses in domestic ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Domestic ducks have been implicated in the dissemination and evolution of H5N1 highly pathogenic avian influenza (HPAI) viruses. Interestingly, the pathogenicity of H5N1 HPAI viruses in domestic ducks has increased over time with some viruses producing 100% mortality in ducks. These changes in vir...

  15. Duck Tembusu virus exhibits neurovirulence in BALB/c mice

    PubMed Central

    2013-01-01

    Background Duck Tembusu virus is a member of the Ntaya group in the genus Flavivirus. The virus has been responsible for severe duck egg-drop syndrome in China since 2010. Its emergence and rapid spread have caused great economic loss for the poultry industry. The epidemiology of the virus infection and the potential threat to public health is of great concern because of the infective and zoonotic nature of flaviviruses. Results In this study, the pathogenicity of duck Tembusu virus in BALB/c mice was investigated. Infected mice developed clinical signs, including loss of appetite, ruffled hair, weight loss, disorientation, blindness and paralysis of hind limbs from six days post- infection following intracerebral inoculation. Morbidity was 100%, with mortality ranging from 20 to 80% in three- to eight-week-old mice. High virus titers were recovered from the brain, and the virus was distributed in several organs. Histologically, there was widespread non-suppurative encephalitis in the brain. Lymphocyte depletion in the spleen was observed, along with fatty degeneration in the liver and kidney. Conclusions Our results demonstrate, for the first time, that duck Tembusu virus is highly neurovirulent in BALB/c mice. The mouse model used in this work was able to produce Tembusu virus infection and could be useful for elucidating some of the aspects of the pathophysiology of other flavivirus infections. PMID:23941427

  16. Pathogenicity and genetic characterization of a duck Tembusu virus associated with egg-dropping in Muscovy ducks.

    PubMed

    Shen, Han-Qin; Lin, Wen-Cheng; Wang, Zhan-Xin; Zhang, Kai; Yan, Zhuan-Qiang; Zhou, Qing-Feng; Qin, Jian-Ping; Xie, Qing-Mei; Bi, Ying-Zuo; Chen, Feng

    2016-09-01

    Duck Tembusu virus (DTMUV) has spread to the major duck-farming region in China, causing acute egg-production drop in Chinese duck population. In this study, we characterized a DTMUV strain (named GD2014) isolated from an egg-production drop duck farm in Guangdong province, South China. The virus was pathogenic to Muscovy duck embryos and caused severe egg production drop for laying Muscovy ducks. The genome sequence of GD2014 shared 97-99% homologies with other waterfowl-origin Tembusu viruses, and shared 89% identities with MM1775 strain isolated from mosquito. Phylogenetic analysis of entire open reading frame (ORF), E gene and NS5 gene indicated that GD2014 belonged to Ntaya group. These results have implications for understanding the orgin, emergence and pathogenicity of DTMUV as well as for the development of vaccines and diagnostics based on epidemiological data. PMID:27354303

  17. Hepatitis C virus. A review.

    PubMed Central

    Tang, E.

    1991-01-01

    Hepatitis C virus has been shown to be responsible for most cases of posttransfusion hepatitis, as well as for sporadic non-A, non-B viral hepatitis. Hepatitis C virus has also been implicated in the development of primary hepatocellular carcinoma, autoimmune hepatitis, and fulminant viral hepatitis. Although the role of the parenteral transmission of hepatitis C virus is well established, its route of transmission in cases of sporadic infection remains unclear. Sexual transmission is suspected but not confirmed. Recent work regarding treatment has shown interferon alfa to be effective, but the discontinuation of therapy is associated with a 50% relapse rate. PMID:1656611

  18. Case report: epithelial intracytoplasmic herpes viral inclusions associated with an outbreak of duck virus enteritis

    USGS Publications Warehouse

    Barr, B.C.; Jessup, David A.; Docherty, Douglas E.; Lownestine, L.J.

    1992-01-01

    Several muscovy ducks from a free-roaming flock of 65 muscovy and mallard ducks died over a 3-week period. Three muscovy ducks were necropsied. Gross and microscopic changes were compatible with duck virus enteritis, and the virus was isolated. In addition to intranuclear viral inclusion bodies in several tissues, intracytoplasmic inclusion bodies were present in esophageal and cloacal epithelium, By electron microscopy, the membrane-bound intracytoplasmic inclusions were found to contain enveloped herpesvirus, and nuclei contained herpes viral nucleocapsids.

  19. The SATE pronucleotide approach applied to acyclovir: part II. Effects of bis(SATE)phosphotriester derivatives of acyclovir on duck hepatitis B virus replication in vitro and in vivo.

    PubMed

    Hantz, O; Périgaud, C; Borel, C; Jamard, C; Zoulim, F; Trépo, C; Imbach, J L; Gosselin, G

    1999-01-01

    The in vitro and in vivo antiviral activities of two mononucleoside phosphotriester derivatives of acyclovir (ACV) incorporating S-acyl-2-thioethyl (SATE) groups are reported using the duck model of hepatitis B (DHBV). In primary duck hepatocyte cultures, the described phosphotriesters significantly inhibited the replication of DHBV at submicromolar concentrations. They were found to be more potent than the parent nucleoside. This result was in agreement with our data concerning the anti-HBV activity of these pronucleotides in HepG2.2.15 cells (previous paper). In vivo, the studied SATE pronucleotide was also found to be more efficient than ACV in infected ducklings upon short-term oral therapy, while intraperitoneal treatment showed high anti-DHBV activity with both ACV and its SATE pronucleotide in this animal model. These findings demonstrate the potential of SATE pronucleotides of ACV as anti-HBV agents. PMID:10027652

  20. Airborne Transmission of a Novel Tembusu Virus in Ducks

    PubMed Central

    Li, Xuesong; Shi, Ying; Liu, Qinfang; Wang, Ying; Li, Guoxin; Teng, Qiaoyang; Zhang, Yuee; Liu, Sidang

    2015-01-01

    The routes of transmission of a newly emerged Tembusu virus (TMUV, Flavivirus) in ducks in China remain unclear. Our epidemiological data show that TMUV is spread in winter, when mosquitos are inactive, which suggests that nonvector transmission routes are involved in the spread of TMUV. Furthermore, in vivo studies indicate that TMUV can be transmitted efficiently among ducks by both direct contact and aerosol transmission. This finding has important implications for the control of infection with this novel TMUV in the field. PMID:26063866

  1. Hepatitis virus panel

    MedlinePlus

    Hepatitis A antibody test; Hepatitis B antibody test; Hepatitis C antibody test; Hepatitis D antibody test ... or past infection, or immunity to hepatitis A Hepatitis B tests: Hepatitis B surface antigen (HBsAg), you have ...

  2. Hepatitis C Virus.

    PubMed

    Kim, Arthur

    2016-09-01

    This issue provides a clinical overview of hepatitis C virus, focusing on transmission, prevention, screening, diagnosis, evaluation, and treatment. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of additional science writers and physician writers. PMID:27595226

  3. Avian influenza virus-induced regulation of duck fibroblast gene expression

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Highly pathogenic avian influenza (HPAI) H5N1 viruses have been non-pathogenic in ducks causing no disease or mild respiratory infections. However, in 2002, new viruses emerged causing systemic disease and death. To better understand the differences in pathogenicity of HPAI viruses in ducks, we in...

  4. Gene expression responses to highly pathogenic avian influenza H5N1 virus infections in ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Differences in host response to infection with avian influenza (AI) viruses were investigated by identifying genes differentially expressed in tissues of infected ducks. Clear differences in pathogenicity were observed among ducks inoculated with five H5N1 HPAI viruses. Virus titers in tissues cor...

  5. Pathogenicity of H5N1 HPAI viruses from Vietnam in chickens and ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ducks and other wild aquatic birds are the natural reservoir of influenza type A viruses, and influenza viruses in these species normally is an asymptomatic infection. Even the viruses that are highly pathogenic for chickens typically can infect but do not cause disease in domestic ducks. However,...

  6. Determinants of pathogenicity of H5N1 highly pathogenic avian influenza viruses in ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ducks have been implicated in the dissemination and evolution of the H5N1 highly pathogenic avian influenza (HPAI) viruses. The pathogenicity of H5N1 HPAI viruses in domestic ducks has increased over time with some viruses producing 100% mortality in very short time. The determinants of pathogenic...

  7. Hepatitis virus panel

    MedlinePlus

    Hepatitis A antibody test; Hepatitis B antibody test; Hepatitis C antibody test; Hepatitis D antibody test ... There are different tests for hepatitis A and B. A positive test is ... may mean: You currently have a hepatitis infection. This may ...

  8. Hepatitis E Virus Infection

    PubMed Central

    Dalton, Harry R.; Abravanel, Florence; Izopet, Jacques

    2014-01-01

    SUMMARY Hepatitis E virus (HEV) infection is a worldwide disease. An improved understanding of the natural history of HEV infection has been achieved within the last decade. Several reservoirs and transmission modes have been identified. Hepatitis E is an underdiagnosed disease, in part due to the use of serological assays with low sensitivity. However, diagnostic tools, including nucleic acid-based tests, have been improved. The epidemiology and clinical features of hepatitis E differ between developing and developed countries. HEV infection is usually an acute self-limiting disease, but in developed countries it causes chronic infection with rapidly progressive cirrhosis in organ transplant recipients, patients with hematological malignancy requiring chemotherapy, and individuals with HIV. HEV also causes extrahepatic manifestations, including a number of neurological syndromes and renal injury. Acute infection usually requires no treatment, but chronic infection should be treated by reducing immunosuppression in transplant patients and/or the use of antiviral therapy. In this comprehensive review, we summarize the current knowledge about the virus itself, as well as the epidemiology, diagnostics, natural history, and management of HEV infection in developing and developed countries. PMID:24396139

  9. The role of NS protein in the pathogenicity of HPAI H5N1 viruses in ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Until 2002, highly pathogenic avian influenza (HPAI) H5N1 viruses caused no disease or only mild respiratory infections in ducks. Since then, new viruses have emerged that cause systemic disease and high mortality in ducks and other waterfowl. Studies on HPAI virus pathogenicity in ducks have been...

  10. The effect of NS1 gene exchange on the pathogenicity of H5N1 HPAI viruses in ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Until 2002, H5N1 highly pathogenic avian influenza (HPAI) viruses caused only mild respiratory infections in ducks. Since then, new viruses have emerged that cause systemic disease and high mortality in ducks and other waterfowl. Studies on HPAI virus pathogenicity in ducks have been limited and t...

  11. Duck egg-drop syndrome caused by BYD virus, a new Tembusu-related flavivirus.

    PubMed

    Su, Jingliang; Li, Shuang; Hu, Xudong; Yu, Xiuling; Wang, Yongyue; Liu, Peipei; Lu, Xishan; Zhang, Guozhong; Hu, Xueying; Liu, Di; Li, Xiaoxia; Su, Wenliang; Lu, Hao; Mok, Ngai Shing; Wang, Peiyi; Wang, Ming; Tian, Kegong; Gao, George F

    2011-01-01

    Since April 2010, a severe outbreak of duck viral infection, with egg drop, feed uptake decline and ovary-oviduct disease, has spread around the major duck-producing regions in China. A new virus, named BYD virus, was isolated in different areas, and a similar disease was reproduced in healthy egg-producing ducks, infecting with the isolated virus. The virus was re-isolated from the affected ducks and replicated well in primary duck embryo fibroblasts and Vero cells, causing the cytopathic effect. The virus was identified as an enveloped positive-stranded RNA virus with a size of approximately 55 nm in diameter. Genomic sequencing of the isolated virus revealed that it is closely related to Tembusu virus (a mosquito-borne Ntaya group flavivirus), with 87-91% nucleotide identity of the partial E (envelope) proteins to that of Tembusu virus and 72% of the entire genome coding sequence with Bagaza virus, the most closely related flavivirus with an entirely sequenced genome. Collectively our systematic studies fulfill Koch's postulates, and therefore, the causative agent of the duck egg drop syndrome occurring in China is a new flavivirus. Flavivirus is an emerging and re-emerging zoonotic pathogen and BYD virus that causes severe egg-drop, could be disastrous for the duck industry. More importantly its public health concerns should also be evaluated, and its epidemiology should be closely watched due to the zoonotic nature of flaviviruses. PMID:21455312

  12. Duck Egg-Drop Syndrome Caused by BYD Virus, a New Tembusu-Related Flavivirus

    PubMed Central

    Yu, Xiuling; Wang, Yongyue; Liu, Peipei; Lu, Xishan; Zhang, Guozhong; Hu, Xueying; Liu, Di; Li, Xiaoxia; Su, Wenliang; Lu, Hao; Mok, Ngai Shing; Wang, Peiyi; Wang, Ming; Tian, Kegong; Gao, George F.

    2011-01-01

    Since April 2010, a severe outbreak of duck viral infection, with egg drop, feed uptake decline and ovary-oviduct disease, has spread around the major duck-producing regions in China. A new virus, named BYD virus, was isolated in different areas, and a similar disease was reproduced in healthy egg-producing ducks, infecting with the isolated virus. The virus was re-isolated from the affected ducks and replicated well in primary duck embryo fibroblasts and Vero cells, causing the cytopathic effect. The virus was identified as an enveloped positive-stranded RNA virus with a size of approximately 55 nm in diameter. Genomic sequencing of the isolated virus revealed that it is closely related to Tembusu virus (a mosquito-borne Ntaya group flavivirus), with 87–91% nucleotide identity of the partial E (envelope) proteins to that of Tembusu virus and 72% of the entire genome coding sequence with Bagaza virus, the most closely related flavivirus with an entirely sequenced genome. Collectively our systematic studies fulfill Koch's postulates, and therefore, the causative agent of the duck egg drop syndrome occurring in China is a new flavivirus. Flavivirus is an emerging and re-emerging zoonotic pathogen and BYD virus that causes severe egg-drop, could be disastrous for the duck industry. More importantly its public health concerns should also be evaluated, and its epidemiology should be closely watched due to the zoonotic nature of flaviviruses. PMID:21455312

  13. Pathobiology of Asian highly pathogenic avian influenza H5N1 virus infection in ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ducks and other wild aquatic birds are the natural reservoir of influenza type A viruses which normally are nonpathogenic in these birds. However, the Asian H5N1 avian influenza (AI) viruses have evolved from producing no disease or mild respiratory infections in ducks, to some strains producing se...

  14. Increased virulence in ducks of H5N1 highly pathogenic avian influenza viruses from Egypt

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The pathogenicity of H5N1 highly pathogenic avian influenza (HPAI) viruses in domestic ducks has increased over time. These changes in virulence have been reported with viruses from countries with high population of domestic ducks. Since 2006, H5N1 HPAI outbreaks in Egypt have been occurring in po...

  15. INCREASED PATHOGENICITY OF H5N1 VIETNAM VIRUSES IN DUCKS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ducks and other wild aquatic birds are the natural reservoir of influenza type A viruses, which usually are nonpathogenic in these birds. The Asian H5N1 HPAI viruses have changed from producing a mild respiratory infection in ducks to some strains causing systemic disease and death. In order to furt...

  16. Pathogenicity of reassortant H5N1 highly pathogenic avian influenza viruses in domestic ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The pathogenicity of H5N1 highly pathogenic avian influenza (HPAI) viruses in domestic ducks has increased over time. These changes in virulence have been reported with viruses from countries with high population of domestic ducks, including Egypt. In order to understand which viral genes are contri...

  17. Studies on vertical and horizontal transmission of duck plague virus in apparently healthy waterfowl

    USGS Publications Warehouse

    Burgess, Elizabeth C.

    1978-01-01

    Healthy waterfowl were found to be carriers of duck plague (DP) virus. Black ducks (Anas rubripes) and Canada geese (Branta canadensis) surviving a natural outbreak of DP at Coloma, Wisconsin, in 1973 yielded DP virus in cloacal swabs taken four years postinfection. Experimental infection of previously unexposed mallard ducks (Anas platyrhynochos) with the Coloma strain of DP virus CO-WI (73) also produced cloacal virus shedding for up to four years after infection. A second DP virus strain, LA-SD (73) from the Lake Andes, South Dakota, epornitic, was detected from cloacal swabs of pintail ducks (Anas acuta), gadwall ducks (Anas strepera), wood ducks (Aix sponsa), and Canada geese infected experimentally one year before. The frequency of swabs positive for DP virus varied between individuals within each of the tested species. The amount of detectable DP virus shed was about 100 plaqueforming units of virus percloacal swab. Oral erosions were present in all species tested except Canada geese and gadwall ducks. Erosions occurred at the openings of the sublingual salivary gland ducts. DP virus was isolated from erosions. All ducks with lesions proved to shed DP virus, although not necessarily at the time they had the lesion. Three pintail ducks treated with dexamethasone for ten days, shed DP virus daily for 19 days after the first day of treatment. These birds also shed DP virus the one time they were tested prior to dexamethosone treatment. An acute lethal outbreak occurred in CO-WI (73) carrier birds. Both DP virus and specific lesions were found in dead birds. The deaths coincided with a change in housing and with the simultaneous introduction of co-housed LA-SD (73) infected ducklings. DP virus was isolated from the chorio-allantoic (CA) fluid of a fourteen day pekin embryo and from five of ten infertile pekin eggs laid by DP carrier birds.

  18. A Duck Enteritis Virus-Vectored Bivalent Live Vaccine Provides Fast and Complete Protection against H5N1 Avian Influenza Virus Infection in Ducks ▿ † §

    PubMed Central

    Liu, Jinxiong; Chen, Pucheng; Jiang, Yongping; Wu, Li; Zeng, Xianying; Tian, Guobin; Ge, Jinying; Kawaoka, Yoshihiro; Bu, Zhigao; Chen, Hualan

    2011-01-01

    Ducks play an important role in the maintenance of highly pathogenic H5N1 avian influenza viruses (AIVs) in nature, and the successful control of AIVs in ducks has important implications for the eradication of the disease in poultry and its prevention in humans. The inactivated influenza vaccine is expensive, labor-intensive, and usually needs 2 to 3 weeks to induce protective immunity in ducks. Live attenuated duck enteritis virus (DEV; a herpesvirus) vaccine is used routinely to control lethal DEV infections in many duck-producing areas. Here, we first established a system to generate the DEV vaccine strain by using the transfection of overlapping fosmid DNAs. Using this system, we constructed two recombinant viruses, rDEV-ul41HA and rDEV-us78HA, in which the hemagglutinin (HA) gene of the H5N1 virus A/duck/Anhui/1/06 was inserted and stably maintained within the ul41 gene or between the us7 and us8 genes of the DEV genome. Duck studies indicated that rDEV-us78HA had protective efficacy similar to that of the live DEV vaccine against lethal DEV challenge; importantly, a single dose of 106 PFU of rDEV-us78HA induced complete protection against a lethal H5N1 virus challenge in as little as 3 days postvaccination. The protective efficacy against both lethal DEV and H5N1 challenge provided by rDEV-ul41HA inoculation in ducks was slightly weaker than that provided by rDEV-us78HA. These results demonstrate, for the first time, that recombinant DEV is suitable for use as a bivalent live attenuated vaccine, providing rapid protection against both DEV and H5N1 virus infection in ducks. PMID:21865383

  19. Identification and genomic analysis of two duck-origin Tembusu virus strains in southern China.

    PubMed

    Li, Linlin; An, Hejia; Sun, Minhua; Dong, Jiawen; Yuan, Jianfeng; Hu, Qilin

    2012-08-01

    Egg-laying duck flocks in Guangdong province, southern China, have been suffering a widely spreading infectious disease with abrupt egg drops and death since the winter of 2010. However, the causative pathogen was not known. We obtained two independent virus isolates named FS and JM from the diseased layer duck flocks and identified them as duck-origin Tembusu virus by PCR detection, sequencing the entire length of the open reading frames (ORFs). The two isolates FS and JM shared high sequence similarity to the isolates of duck-origin Tembusu virus that was first emerged in eastern China in April 2010. Blast analysis shows that the whole ORF sequences of FS and JM have the highest similarity (>99 %) to BYD-1(the first reported duck-origin Tembusu virus) and JS804 (the first reported goose-origin Tembusu virus), indicating that the full-length genomes were highly conserved in waterfowl-origin Tembusu viruses. The present study suggests that duck-origin Tembusu viruses have spread fast from eastern China to southern China, causing widely spreading infections. The high conservation of duck-origin Tembusu virus strains provides the genomic basis for choosing the strains for vaccine preparation for better protection against this new virus infection. PMID:22581444

  20. Transmission Dynamics of the Recently-Identified BYD Virus Causing Duck Egg-Drop Syndrome

    PubMed Central

    Vaidya, Naveen K.; Wang, Feng-bin; Zou, Xingfu; Wahl, Lindi M.

    2012-01-01

    Baiyangdian (BYD) virus is a recently-identified mosquito-borne flavivirus that causes severe disease in ducks, with extremely rapid transmission, up to 15% mortality within 10 days and 90% reduction in egg production on duck farms within 5 days of infection. Because of the zoonotic nature of flaviviruses, the characterization of BYD virus and its epidemiology are important public health concerns. Here, we develop a mathematical model for the transmission dynamics of this novel virus. We validate the model against BYD outbreak data collected from duck farms in Southeast China, as well as experimental data obtained from an animal facility. Based on our model, the basic reproductive number of BYD virus is high (R0 = 21) indicating that this virus is highly transmissible, consistent with the dramatic epidemiology observed in BYDV-affected duck farms. Our results indicate that younger ducks are more vulnerable to BYD disease and that ducks infected with BYD virus reduce egg production (to about 33% on average) for about 3 days post-infection; after 3 days infected ducks are no longer able to produce eggs. Using our model, we predict that control measures which reduce contact between mosquitoes and ducks such as mosquito nets are more effective than insecticides. PMID:22529985

  1. Transmission dynamics of the recently-identified BYD virus causing duck egg-drop syndrome.

    PubMed

    Vaidya, Naveen K; Wang, Feng-bin; Zou, Xingfu; Wahl, Lindi M

    2012-01-01

    Baiyangdian (BYD) virus is a recently-identified mosquito-borne flavivirus that causes severe disease in ducks, with extremely rapid transmission, up to 15% mortality within 10 days and 90% reduction in egg production on duck farms within 5 days of infection. Because of the zoonotic nature of flaviviruses, the characterization of BYD virus and its epidemiology are important public health concerns. Here, we develop a mathematical model for the transmission dynamics of this novel virus. We validate the model against BYD outbreak data collected from duck farms in Southeast China, as well as experimental data obtained from an animal facility. Based on our model, the basic reproductive number of BYD virus is high (R(0) = 21) indicating that this virus is highly transmissible, consistent with the dramatic epidemiology observed in BYDV-affected duck farms. Our results indicate that younger ducks are more vulnerable to BYD disease and that ducks infected with BYD virus reduce egg production (to about 33% on average) for about 3 days post-infection; after 3 days infected ducks are no longer able to produce eggs. Using our model, we predict that control measures which reduce contact between mosquitoes and ducks such as mosquito nets are more effective than insecticides. PMID:22529985

  2. SURVEY FOR WEST NILE VIRUS ANTIBODIES IN WILD DUCKS, 2004-06, USA.

    PubMed

    Hofmeister, Erik K; Jankowski, Mark D; Goldberg, Diana; Franson, J Christian

    2016-04-28

    Detection of West Nile virus (WNV) in ducks has been reported in North America in isolated cases of mortality in wild waterbirds and following outbreaks in farmed ducks. Although the virus has been noted as an apparent incidental finding in several species of ducks, little is known about the prevalence of exposure or the outcome of infection with WNV in wild ducks in North America. From 2004-06, we collected sera from 1,406 wild-caught American Wigeon ( Anas americana ), Mallard ( Anas platyrhynchos ), and Northern Pintail ( Anas acuta ) ducks at national wildlife refuges (NWRs) in North Dakota and Wood Ducks ( Aix sponsa ) at NWRs in South Carolina and Tennessee. We measured the prevalence of previous exposure to WNV in these ducks by measuring WNV antibodies and evaluated variation in exposure among species, age, and year. Additionally, we evaluated the performance of a commercial antibody to wild bird immunoglobulin in duck species that varied in their phylogenetic relatedness to the bird species the antibody was directed against. As determined by a screening immunoassay and a confirmatory plaque reduction neutralization assay, the prevalence of WNV antibody was 10%. In light of experimental studies that show ducks to be relatively resistant to mortality caused by WNV, the antibody prevalence we detected suggests that wild ducks may be less-frequently exposed to WNV than expected for birds inhabiting wetlands where they may acquire infection from mosquitoes. PMID:26981693

  3. Survey for West Nile virus antibodies in wild ducks, 2004-06, USA

    USGS Publications Warehouse

    Hofmeister, Erik K.; Jankowski, Mark D.; Goldberg, Diana R.; Franson, J. Christian

    2016-01-01

    Detection of West Nile virus (WNV) in ducks has been reported in North America in isolated cases of mortality in wild waterbirds and following outbreaks in farmed ducks. Although the virus has been noted as an apparent incidental finding in several species of ducks, little is known about the prevalence of exposure or the outcome of infection with WNV in wild ducks in North America. From 2004–06, we collected sera from 1,406 wild-caught American Wigeon (Anas americana), Mallard (Anas platyrhynchos), and Northern Pintail (Anas acuta) ducks at national wildlife refuges (NWRs) in North Dakota and Wood Ducks (Aix sponsa) at NWRs in South Carolina and Tennessee. We measured the prevalence of previous exposure to WNV in these ducks by measuring WNV antibodies and evaluated variation in exposure among species, age, and year. Additionally, we evaluated the performance of a commercial antibody to wild bird immunoglobulin in duck species that varied in their phylogenetic relatedness to the bird species the antibody was directed against. As determined by a screening immunoassay and a confirmatory plaque reduction neutralization assay, the prevalence of WNV antibody was 10%. In light of experimental studies that show ducks to be relatively resistant to mortality caused by WNV, the antibody prevalence we detected suggests that wild ducks may be less-frequently exposed to WNV than expected for birds inhabiting wetlands where they may acquire infection from mosquitoes.

  4. Experimental susceptibility of Wood Ducks (Aix sponsa) for West Nile virus

    USGS Publications Warehouse

    Hofmeister, Erik K.; Porter, Robert E.; Franson, J. Christian

    2015-01-01

    Detection of West Nile virus (WNV) has been reported in a variety of wild ducks in the US, but little is known about the pathogenesis and outcome of exposure of the disease in these species. Previous experimental studies of WNV in ducks either have challenged a small number of ducks with WNV or have tested domesticated ducks. To determine susceptibility and immune response, we challenged 7-wk-old Wood Ducks (Aix sponsa) with a 1999 American Crow (Corvus brachyrhynchos) isolate of WNV. Wood Ducks were susceptible to infection with the virus, and, although clinical signs or mortality were not observed, microscopic lesions were noted, particularly in the heart and brain. West Nile virus viremia peaked on day 2 postinfection (pi) at 104.54 plaque-forming units (PFU) of virus/mL serum and WNV was shed orally (between 102and 102.9 PFU per swab) and cloacally. Specific anti-WNV antibody response was rapid, with anti-WNV IgM detected on day 3 pi followed on day 5 pi by anti-WNV IgG. Neutralizing antibodies were detected by plaque-reduction neutralization assay in one duck on day 4 pi, and in all sampled ducks on day 5. These results indicate that Wood Ducks are susceptible to WNV, but it is unlikely that significant WNV mortality events occur in Wood Ducks or that ducks play a significant role in transmission. However, WNV viremia was sufficient, in theory, to infect mosquitoes, and oral and cloacal shedding of the virus may increase the risk of infection to other waterbirds.

  5. Duck Interferon-Inducible Transmembrane Protein 3 Mediates Restriction of Influenza Viruses

    PubMed Central

    Blyth, Graham A. D.; Chan, Wing Fuk; Webster, Robert G.

    2015-01-01

    ABSTRACT Interferon-inducible transmembrane proteins (IFITMs) can restrict the entry of a wide range of viruses. IFITM3 localizes to endosomes and can potently restrict the replication of influenza A viruses (IAV) and several other viruses that also enter host cells through the endocytic pathway. Here, we investigate whether IFITMs are involved in protection in ducks, the natural host of influenza virus. We identify and sequence duck IFITM1, IFITM2, IFITM3, and IFITM5. Using quantitative PCR (qPCR), we demonstrate the upregulation of these genes in lung tissue in response to highly pathogenic IAV infection by 400-fold, 30-fold, 30-fold, and 5-fold, respectively. We express each IFITM in chicken DF-1 cells and show duck IFITM1 localizes to the cell surface, while IFITM3 localizes to LAMP1-containing compartments. DF-1 cells stably expressing duck IFITM3 (but not IFITM1 or IFITM2) show increased restriction of replication of H1N1, H6N2, and H11N9 IAV strains but not vesicular stomatitis virus. Although duck and human IFITM3 share only 38% identity, critical residues for viral restriction are conserved. We generate chimeric and mutant IFITM3 proteins and show duck IFITM3 does not require its N-terminal domain for endosomal localization or antiviral function; however, this N-terminal end confers endosomal localization and antiviral function on IFITM1. In contrast to mammalian IFITM3, the conserved YXXθ endocytosis signal sequence in the N-terminal domain of duck IFITM3 is not essential for correct endosomal localization. Despite significant structural and amino acid divergence, presumably due to host-virus coevolution, duck IFITM3 is functional against IAV. IMPORTANCE Immune IFITM genes are poorly conserved across species, suggesting that selective pressure from host-specific viruses has driven this divergence. We wondered whether coevolution between viruses and their natural host would result in the evasion of IFITM restriction. Ducks are the natural host of avian

  6. Unraveling hepatitis C virus structure.

    PubMed

    Fauvelle, Catherine; Felmlee, Daniel J; Baumert, Thomas F

    2014-04-01

    The high variability and the limited knowledge of the structure of the hepatitis C virus (HCV) envelope glycoproteins (GP) are challenging hurdles for vaccine design. Recently, Kong et al. published a new model of HCV E2 GP structure in Science, revealing a globular structure, starkly contrasting from the extended model of class II fusion proteins from other Flaviviridae viruses. PMID:24626133

  7. The effect of Tembusu virus infection in different week-old Cherry Valley breeding ducks.

    PubMed

    Lu, Yunjian; Dou, Yanguo; Ti, Jinfeng; Wang, Aihua; Cheng, Binghua; Zhang, Xin; Diao, Youxiang

    2016-08-30

    To study the effect of Tembusu virus (TMUV) infection on Cherry Valley Breeding ducks of different ages, 350 five-week-old ducks were divided into 14 groups. Ducks in seven experimental group were respectively infected with 1.265×10(5) mean embryo lethal dose (ELD50) of TMUV-AHQY strain (in 4.2mL) by intravenous route. Ducks in control groups were inoculated with Phosphate-buffered Saline (PBS) in the same way. Clinical symptoms, gross and microscopic lesions, viral loads and serum antibodies were detected and recorded for 20days after infection. Some ducks infected at 7 and 21 week s of age showed severe clinical symptoms including depression and inappetence, and no obvious clinical symptoms were seen in other week-old infected ducks. Severe gross lesions including hepatomegaly, meningeal congestion, myocardial hemorrhage, intestinal, myocardial and pulmonary edema were observed in ducks infected at 7, 18 and 21 weeks of age. No or mild gross lesions were observed in ducks infected at 14 and 16 weeks of age. The main microscopic lesions including hyperaemia, degeneration and necrosis of different cells and inflammatory cellular infiltration mainly consisting of mononuclear cells or lymphocytes were observed in ducks infected at 7 and 21 week of age. But relatively intact structures and rare lymphocytic infiltration were presented in ducks infected at 14 and 16 weeks of age. Viral antigen was more frequently observed in organ slices collected from 7 week-old infected ducks and few positive staining was found in 14 and 16 week-old infected ducks. Less viral loads in different tissues and swabs were detected by a quantitative real-time PCR assay. The level of viral loads in the tissues of ducks infected at 14 and 16 weeks of age was very lower than that of ducks infected at 7 and 21 weeks of age. Meanwhile, less viral copy numbers were detected in swab samples collected from 14 and 16 week-old infected ducks. Ducks infected at 14-week-old developed significantly

  8. Hepatitis B virus morphogenesis

    PubMed Central

    Bruss, Volker

    2007-01-01

    The hepatitis B virus (HBV) particle consists of an envelope containing three related surface proteins and probably lipid and an icosahedral nucleocapsid of approximately 30 nm diameter enclosing the viral DNA genome and DNA polymerase. The capsid is formed in the cytosol of the infected cell during packaging of an RNA pregenome replication complex by multiple copies of a 21-kDa C protein. The capsid gains the ability to bud during synthesis of the viral DNA genome by reverse transcription of the pregenome in the lumen of the particle. The three envelope proteins S, M, and L shape a complex transmembrane fold at the endoplasmic reticulum, and form disulfide-linked homo- and heterodimers. The transmembrane topology of a fraction of the large envelope protein L changes post-translationally, therefore, the N terminal domain of L (preS) finally appears on both sides of the membrane. During budding at an intracellular membrane, a short linear domain in the cytosolic preS region interacts with binding sites on the capsid surface. The virions are subsequently secreted into the blood. In addition, the surface proteins can bud in the absence of capsids and form subviral lipoprotein particles of 20 nm diameter which are also secreted. PMID:17206755

  9. Quantitative Proteomic Analysis of Duck Ovarian Follicles Infected with Duck Tembusu Virus by Label-Free LC-MS

    PubMed Central

    Han, Kaikai; Zhao, Dongmin; Liu, Yuzhuo; Liu, Qingtao; Huang, Xinmei; Yang, Jing; An, Fengjiao; Li, Yin

    2016-01-01

    Duck Tembusu virus (DTMUV) is a newly emerging pathogenic flavivirus that has caused massive economic losses to the duck industry in China. DTMUV infection mainly results in significant decreases in egg production in egg-laying ducks within 1–2 weeks post infection. However, information on the comparative protein expression of host tissues in response to DTMUV infection is limited. In the present study, the cellular protein response to DTMUV infection in duck ovarian follicles was analyzed using nano-flow high-performance liquid chromatography-electrospray tandem mass spectrometry. Quantitative proteomic analysis revealed 131 differentially expressed proteins, among which 53 were up regulated and 78 were down regulated. The identified proteins were involved in the regulation of essential processes such as cellular structure and integrity, RNA processing, protein biosynthesis and modification, vesicle transport, signal transduction, and mitochondrial pathway. Some selected proteins that were found to be regulated in DTMUV-infected tissues were screened by quantitative real-time PCR to examine their regulation at the transcriptional level, western blot analysis was used to validate the changes of some selected proteins on translational level. To our knowledge, this study is the first to analyze the proteomic changes in duck ovarian follicles following DTMUV infection. The protein-related information obtained in this study may be useful to understand the host response to DTMUV infection and the inherent mechanism of DTMUV replication and pathogenicity. PMID:27066001

  10. Use of muscovy duck embryo fibroblasts for the isolation of viruses from wild birds

    USGS Publications Warehouse

    Docherty, D.E.; Slota, Paul G.

    1988-01-01

    Techniques are described for the preparation, cryopreservation, and inoculation of Muscovy duck embryo cell cultures. The procedure yields a susceptible reproducible cell culture system for the isolation and cultivation of viruses from wild birds.

  11. Hepatitis virus vaccines: present status.

    PubMed Central

    Krugman, S.

    1982-01-01

    During the past decade there has been extraordinary progress toward the development of vaccines for the prevention of type A and type B hepatitis. The successful propagation of hepatitis A virus in cell culture in 1979 was followed by the preparation of experimental live attenuated hepatitis A vaccines that have been shown to induce antibody in marmosets and chimpanzees and protect immunized marmosets against challenge with hepatitis A virus. The first human immunization trials will begin in mid-1982. An inactivated hepatitis B vaccine that was licensed in the United States in November 1981 has been shown to be safe, immunogenic, and effective. When this vaccine becomes available for use in July 1982, it will be recommended for persons who are considered to be at increased risk of contracting hepatitis B infection. Future generations of hepatitis B vaccines may be prepared from hepatitis B surface antigen derived from DNA recombinant technology or by in vitro synthesis of HBs Ag determinants by chemical means. PMID:6295013

  12. Effect of age on pathogenesis and innate immune responses in Pekin ducks infected with different H5N1 highly pathogenic avian influenza viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The pathogenicity of H5N1 highly pathogenic avian influenza (HPAI) viruses in domestic ducks varies between different viruses and is affected by the age of the ducks, with younger ducks presenting more severe disease. In order to better understand the pathobiology of H5N1 HPAI in ducks, including t...

  13. The pathobiology of highly pathogenic H5N2 avian influenza virus in Ruddy ducks and Lesser Scaup

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The susceptibility and pathogenesis of avian influenza virus (AIV) has not been characterized in numerous duck species, especially diving ducks, some of which migrate across the continental U.S. The pathobiology of highly pathogenic (HP) H5N2 AIV was characterized in two diving duck species, Ruddy ...

  14. Phylogenetic and Pathotypical Analysis of Two Virulent Newcastle Disease Viruses Isolated from Domestic Ducks in China

    PubMed Central

    Zhang, Shouping; Wang, Xiaoting; Zhao, Changguang; Liu, Dehua; Hu, Yanxin; Zhao, Jixun; Zhang, Guozhong

    2011-01-01

    Two velogenic Newcastle disease viruses (NDV) obtained from outbreaks in domestic ducks in China were characterized in this study. Phylogenetic analysis revealed that both strains clustered with the class II viruses, with one phylogenetically close to the genotype VII NDVs and the other closer to genotype IX. The deduced amino acid sequence of the cleavage site of the fusion (F) protein confirmed that both isolates contained the virulent motif 112RRQK/RRF117 at the cleavage site. The two NDVs had severe pathogenicity in fully susceptible chickens, resulting in 100% mortality. One of the isolates also demonstrated some pathogenicity in domestic ducks. The present study suggests that more than one genotype of NDV circulates in domestic ducks in China and viral transmission may occur among chickens and domestic ducks. PMID:21949828

  15. Hepatitis D Virus: A Call to Screening

    PubMed Central

    Ahn, Joseph

    2014-01-01

    Hepatitis D virus causes an aggressive viral hepatitis with a virulent course of progression to cirrhosis and hepatic decompensation. It relies on hepatitis B coinfection for its pathogenesis and propagation. Hepatitis D virus had become the forgotten virus, with reduced public awareness, medical interest, and research support. Recently, there has been a resurgence of awareness and interest in hepatitis D, with improvements in diagnostic testing and establishment of international collaborative efforts to improve therapy. This article provides a framework to understand the impetus for increased screening as well as to identify key issues toward which collaborative efforts can be directed.

  16. Complete Genomic Sequence of a Muscovy Duck-Origin Reticuloendotheliosis Virus from China

    PubMed Central

    Jiang, Tiantian; Lu, Xinhao; Yuan, Yuan; Zheng, Lisha; Shi, Jiajian

    2012-01-01

    The complete proviral sequence of a Muscovy duck-origin reticuloendotheliosis virus (REV) associated with spontaneously occurring neoplastic disease in 2011 in Zhejiang province, China, was determined. Comparative sequence analyses indicate that the present REV is most closely related to the chicken-origin REV isolate HLJR0901 and the goose-origin isolate Goose/3410/06. These findings suggest that chickens or geese may transmit the REV to Muscovy ducks. PMID:23118464

  17. Whole-Genome Sequence of Duck Tembusu Virus Strain DTMUV/CH/2014, Isolated in China

    PubMed Central

    Zhou, Xinrong; Zhang, Tiansheng; Song, Deping; Huang, Tao; Peng, Qi; Chen, Yanjun; Li, Anqi; Zhang, Fanfan; Wu, Qi; Ye, Yu

    2016-01-01

    The whole-complete genome sequence of a strain of duck tembusu virus (DTMUV), DTMUV/CH/2014, affecting layer ducks in China, was determined and characterized. Compared with DTMUV sequences available in GenBank, DTMUV/CH/2014 has 3 amino acid mutations located in the capsid, prM, and NS3 genes of DTMUV/CH/2014. PMID:26823592

  18. Differences in pathogenicity of A/Duck/Vietnam/201/05 H5N1 highly pathogenic avian influenza virus reassortants in ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In order to understand which viral genes contribute to the high virulence of A/Dk/Vietnam/201/05 H5N1 highly pathogenic avian influenza (HPAI) virus in ducks, we used reverse genetics to generate single-gene reassortant viruses with genes from A/Ck/Indonesia/7/03, a virus that produces mild disease ...

  19. Identification of morphological differences between avian influenza A viruses grown in chicken and duck cells.

    PubMed

    Al-Mubarak, Firas; Daly, Janet; Christie, Denise; Fountain, Donna; Dunham, Stephen P

    2015-03-01

    Although wild ducks are considered to be the major reservoirs for most influenza A virus subtypes, they are typically resistant to the effects of the infection. In contrast, certain influenza viruses may be highly pathogenic in other avian hosts such as chickens and turkeys, causing severe illness and death. Following in vitro infection of chicken and duck embryo fibroblasts (CEF and DEF) with low pathogenic avian influenza (LPAI) viruses, duck cells die more rapidly and produce fewer infectious virions than chicken cells. In the current study, the morphology of viruses produced from CEF and DEF cells infected with low pathogenic avian H2N3 was examined. Transmission electron microscopy showed that viruses budding from duck cells were elongated, while chicken cells produced mostly spherical virions; similar differences were observed in viral supernatants. Sequencing of the influenza genome of chicken- and duck-derived H2N3 LPAI revealed no differences, implicating host cell determinants as responsible for differences in virus morphology. Both DEF and CEF cells produced filamentous virions of equine H3N8 (where virus morphology is determined by the matrix gene). DEF cells produced filamentous or short filament virions of equine H3N8 and avian H2N3, respectively, even after actin disruption with cytochalasin D. These findings suggest that cellular factors other than actin are responsible for the formation of filamentous virions in DEF cells. The formation of elongated virions in duck cells may account for the reduced number of infectious virions produced and could have implications for virus transmission or maintenance in the reservoir host. PMID:25613009

  20. Innate immune responses to infection with H5N1 highly pathogenic avian influenza virus in different duck species

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ducks have been implicated in the dissemination and evolution of H5N1 highly pathogenic avian influenza (HPAI) viruses. Differences in pathogenicity and response to vaccination have been observed between different duck species. The innate immune system is responsible for controlling viruses during t...

  1. Experimental infection of mallard ducks with different subtype H5 and H7 highly pathogenic avian influenza viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Highly pathogenic avian influenza viruses (HPAIV’s) remain a threat to poultry worldwide. Avian influenza viruses, including HPAIV, are usually non-pathogenic for ducks and other wild aquatic birds, with the exception of some Asian lineage H5N1 HPAIVs which can cause severe disease in ducks. With ...

  2. Development of a highly immunogenic Newcastle disease virus chicken vaccine strain of duck origin.

    PubMed

    Kim, J Y; Kye, S J; Lee, H J; Gaikwad, S; Lee, H S; Jung, S C; Choi, K S

    2016-04-01

    Newcastle disease virus (NDV) strain NDRL0901 was developed as a live vaccine candidate for control of Newcastle disease. NDV isolate KR/duck/13/07 (DK1307) of duck origin was used as the selected vaccine strain. DK1307 was passaged 6 times in chickens. Then a single clone from the chicken-adapted virus (DK1307C) was finally selected, and the vaccine strain was named NDRL0901. DK1307C and the clone NDRL0901 viruses showed enhanced immunogenicity compared to the DK1307 virus. Principal component analysis based on fusion and hemagglutinin-neuraminidase genes revealed the codon usage pattern in the dataset is distinct separating duck viral sequences and avian sequences, and passage of the duck origin virus into the chicken host causes deviation in the codon usage pattern. The NDRL0901 virus was avirulent and did not acquire viral virulence even after 7 back passages in chickens. When day-old chicks were vaccinated with the NDRL0901 virus via spray, eye drops, and drinking water, the vaccinated birds showed no clinical signs and had significant protection efficacy (>80%) against very virulent NDV (Kr005 strain) infection regardless of the administration route employed. The results indicate that the NDRL0901 strain is safe in chickens and can offer protective immunity. PMID:26769266

  3. An infectious disease of ducks caused by a newly emerged Tembusu virus strain in mainland China.

    PubMed

    Yan, Pixi; Zhao, Youshu; Zhang, Xu; Xu, Dawei; Dai, Xiaoguang; Teng, Qiaoyang; Yan, Liping; Zhou, Jiewen; Ji, Xiwen; Zhang, Shumei; Liu, Guangqing; Zhou, Yanjun; Kawaoka, Yoshihiro; Tong, Guangzhi; Li, Zejun

    2011-08-15

    During investigations into an outbreak of egg production decline, retarded growth, and even death among ducks in Southeast China, a novel Tembusu virus strain named Tembusu virus Fengxian 2010 (FX2010) was isolated. This virus replicated in embryonated chicken eggs and caused embryo death. In cross-neutralization tests, antiserum to the partial E protein of Tembusu virus Mm1775 strain neutralized FX2010, whereas antiserum to Japanese encephalitis virus did not. FX2010 is an enveloped RNA virus of approximately 45-50 nm in diameter. Sequence analysis of its E and NS5 genes showed that both genes share up to 99.6% nucleotide sequence identity with Baiyangdian virus, and up to 88% nucleotide sequence identity with their counterparts in Tembusu virus. FX2010 was transmitted without mosquito, and caused systemic infection and lesions in experimentally infected ducks. These results indicate that FX2010 and BYD virus are newly emerged Tembusu virus strains that cause an infectious disease in ducks. PMID:21722935

  4. Experimental co-infections of domestic ducks with a virulent Newcastle disease virus and low or highly pathogenic avian influenza viruses

    PubMed Central

    Pantin-Jackwood, Mary; Costa-Hurtado, Mar; Miller, Patti J.; Afonso, Claudio L.; Spackman, Erica; Kapczynski, Darrell; Shepherd, Eric; Smith, Diane; Swayne, David

    2015-01-01

    Infections with avian influenza viruses (AIV) of low and high pathogenicity (LP and HP) and Newcastle disease virus (NDV) are commonly reported in domestic ducks in many parts of the world. However, it’s not clear if co-infections with these viruses affect the severity of the diseases they produce, the amount of virus shed, and transmission of the viruses. In this study we infected domestic ducks with a virulent NDV virus (vNDV) and either a LPAIV or a HPAIV by giving the viruses individually, simultaneously, or sequentially two days apart. No clinical signs were observed in ducks infected or co-infected with vNDV and LPAIV, but co-infection decreased the number of ducks shedding vNDV and the amount of virus shed (P <0.01) at 4 days post inoculation (dpi). Co-infection didn’t affect the number of birds shedding LPAIV, but more LPAIV was shed at 2 dpi (P <0.0001) from ducks inoculated with only LPAIV compared to ducks co-infected with vNDV. Ducks that received the HPAIV with the vNDV simultaneously survived fewer days (P <0.05) compared to the ducks that received the vNDV two days before the HPAIV. Co-infection also reduced transmission of vNDV to naïve contact ducks housed with the inoculated ducks. In conclusion, domestic ducks can become co-infected with vNDV and LPAIV with no effect on clinical signs but with reduction of virus shedding and transmission. These findings indicate that infection with one virus can interfere with replication of another, modifying the pathogenesis and transmission of the viruses. PMID:25759292

  5. Reassortant influenza A viruses in wild duck populations: effects on viral shedding and persistence in water

    PubMed Central

    Lebarbenchon, Camille; Sreevatsan, Srinand; Lefèvre, Thierry; Yang, My; Ramakrishnan, Muthannan A.; Brown, Justin D.; Stallknecht, David E.

    2012-01-01

    Wild ducks of the genus Anas represent the natural hosts for a large genetic diversity of influenza A viruses. In these hosts, co-infections with different virus genotypes are frequent and result in high rates of genetic reassortment. Recent genomic data have provided information regarding the pattern and frequency of these reassortant viruses in duck populations; however, potential consequences on viral shedding and maintenance in the environment have not been investigated. On the basis of full-genome sequencing, we identified five virus genotypes, in a wild duck population in northwestern Minnesota (USA), that naturally arose from genetic reassortments. We investigated the effects of influenza A virus genotype on the viral shedding pattern in Mallards (Anas platyrhynchos) and the duration of infectivity in water, under different temperature regimens. Overall, we found that variation in the viral genome composition of these isolates had limited effects on duration, extent and pattern of viral shedding, as well as on the reduction of infectivity in water over time. These results support that, in wild ducks, functionally equivalent gene segments could be maintained in virus populations with no fitness costs when genetic reassortments occur. PMID:22859590

  6. Reassortant influenza A viruses in wild duck populations: effects on viral shedding and persistence in water.

    PubMed

    Lebarbenchon, Camille; Sreevatsan, Srinand; Lefèvre, Thierry; Yang, My; Ramakrishnan, Muthannan A; Brown, Justin D; Stallknecht, David E

    2012-10-01

    Wild ducks of the genus Anas represent the natural hosts for a large genetic diversity of influenza A viruses. In these hosts, co-infections with different virus genotypes are frequent and result in high rates of genetic reassortment. Recent genomic data have provided information regarding the pattern and frequency of these reassortant viruses in duck populations; however, potential consequences on viral shedding and maintenance in the environment have not been investigated. On the basis of full-genome sequencing, we identified five virus genotypes, in a wild duck population in northwestern Minnesota (USA), that naturally arose from genetic reassortments. We investigated the effects of influenza A virus genotype on the viral shedding pattern in Mallards (Anas platyrhynchos) and the duration of infectivity in water, under different temperature regimens. Overall, we found that variation in the viral genome composition of these isolates had limited effects on duration, extent and pattern of viral shedding, as well as on the reduction of infectivity in water over time. These results support that, in wild ducks, functionally equivalent gene segments could be maintained in virus populations with no fitness costs when genetic reassortments occur. PMID:22859590

  7. Respiratory tract versus cloacal sampling of migratory ducks for influenza A viruses: are both ends relevant?

    PubMed Central

    Krauss, Scott; Pryor, Sydney Paul; Raven, Garnet; Danner, Angela; Kayali, Ghazi; Webby, Richard J.; Webster, Robert G.

    2012-01-01

    Please cite this paper as: Krauss et al. (2012) Respiratory tract versus cloacal sampling of migratory ducks for influenza A viruses: are both ends relevant? Influenza and Other Respiratory Viruses DOI: . Background  Early studies in dabbling ducks showed that cloacal swabs yielded a larger number of avian influenza virus (AIV) isolates than did respiratory tract swabs. Historically, AIV surveillance has been performed by collecting cloacal or environmental fecal samples only. Highly pathogenic avian influenza H5N1 virus emerged in 1996 and replicated to higher titers in the respiratory rather than the gastrointestinal tract of ducks, prompting the collection of respiratory samples in addition to cloacal swabs from wild birds. Studies confirmed that some virus subtypes, especially H9 and highly pathogenic H5, are shed primarily through the respiratory tract and may not be detected in cloacal swabs. Objectives  To examine prevalence and subtype differences for AIV isolates from cloacal or respiratory swabs of wild ducks and to determine whether individual respiratory tract samples should be included in AIV surveillance studies in wild birds. Methods  Individual respiratory tract and cloacal swabs were collected from each of 1036 wild ducks in Alberta, Canada, during the month of August from 2007 to 2010 in an ongoing surveillance study. Virus isolation in eggs and subtype identification by antigenic and molecular methods were performed. Results and conclusions  Respiratory tract and cloacal swabs yielded ten influenza virus HA subtypes representing 28 HA–NA combinations. Three HA–NA subtype combinations were found exclusively in respiratory tract samples. Only four HA subtypes (H1, H3, H4, and H7) were recovered from respiratory samples, but respiratory shedding was associated with the dominance of 1 year’s subtype. Might respiratory shedding provide a risk assessment indicator? PMID:22458473

  8. Protective effects of recombinant glycoprotein D based prime boost approach against duck enteritis virus in mice model.

    PubMed

    Aravind, S; Kamble, Nitin Machindra; Gaikwad, Satish S; Shukla, Sanjeev Kumar; Saravanan, R; Dey, Sohini; Madhan Mohan, C

    2015-11-01

    Duck virus enteritis, also known as duck plague, is an acute herpes viral infection of ducks caused by duck enteritis virus (DEV). The method of repeated immunization with a live attenuated vaccine has been used for the prevention and control of duck enteritis virus (DEV). However, the incidence of the disease in vaccinated flocks and latency reactivation are the major constraints in the present vaccination programme. The immunogenicity and protective efficacy afforded by intramuscular inoculation of plasmid DNA encoding DEV glycoprotein D (pCDNA-gD) followed by DEV gD expressed in Saccharomyces cerevisia (rgD) was assessed in a murine model. Compared with mice inoculated with DNA (pCDNA-gD) or protein (rgD) only, mice inoculated with the combination of gD DNA and protein had enhanced ELISA antibody titers to DEV and had accelerated clearance of virus following challenge infection. Furthermore, the highest levels of lymphocyte proliferation response, IL-4, IL-12 and IFN-γ production were induced following priming with the DNA vaccine and boosting with the rgD protein. For instance, the specially designed recombinant DEV vector vaccine would be the best choice to use in ducks. It offers an excellent solution to the low vaccination coverage rate in ducks. We expect that the application of this novel vaccine in the near future will greatly decrease the virus load in the environment and reduce outbreaks of DEV in ducks. PMID:26188265

  9. Hepatitis B virus and hepatitis C virus dual infection

    PubMed Central

    Caccamo, Gaia; Saffioti, Francesca; Raimondo, Giovanni

    2014-01-01

    Hepatitis B virus (HBV) and hepatitis C virus (HCV) share common mode of transmission and both are able to induce a chronic infection. Dual HBV/HCV chronic coinfection is a fairly frequent occurrence, especially in high endemic areas and among individuals at high risk of parenterally transmitted infections. The intracellular interplay between HBV and HCV has not yet been sufficiently clarified, also due to the lack of a proper in vitro cellular model. Longitudinal evaluation of serum HBV DNA and HCV RNA amounts has revealed that complex virological profiles may be present in coinfected patients. Dual HBV/HCV infection has been associated to a severe course of the liver disease and to a high risk of developing hepatocellular carcinoma. Despite the clinical importance, solid evidence and clear guidelines for treatment of this special population are still lacking. This review summarizes the available data on the virological and clinical features as well as the therapeutic options of the dual HBV/HCV infection, and highlights the aspects that need to be better clarified. PMID:25356020

  10. [Hepatitis due to herpes group viruses].

    PubMed

    Cisneros-Herreros, José M; Herrero-Romero, Marta

    2006-01-01

    In immunocompetent patients, primary infection by herpes simplex virus (HSV), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6, and Epstein-Barr virus (EBV) generally produces mild, self-limited hepatitis. Primary infection by HSV in neonates and pregnant women, and infection by VZV in hematological and bone marrow recipients can cause fulminant hepatitis without characteristic skin lesions. In liver transplant recipients, hepatitis is the most common expression of CMV infection and the related symptoms are indistinguishable from those of acute rejection. Persistent hepatitis is a manifestation of the syndrome of active chronic infection by the EBV. Fulminating hepatitis due to herpes virus can be treated effectively if therapy is started early; hence, a high degree of clinical suspicion and inclusion of herpes virus in the differential diagnosis of this syndrome is necessary. PMID:16792943

  11. Differential growth of avian influenza virus in chicken and duck cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ducks and chickens infected with AI viruses display clear differences in disease manifestation. To understand the mechanisms responsible for these differences we have determined the ability of several AI isolates to replicate in primary tracheal epithelial cells and fibroblasts from both species. Re...

  12. Complete genome sequence of a genotype XVII Newcastle disease virus, isolated from an apparently healthy domestic duck in Nigeria

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The first complete genome sequence of a strain of Newcastle disease virus (NDV) of genotype XVII is described here. A velogenic strain (duck/Nigeria/903/KUDU-113/1992) was isolated from an apparently healthy free-roaming domestic duck sampled in Kuru, Nigeria, in 1992. Phylogenetic analysis of the f...

  13. Characterization and Sequencing of a Genotype VIId Newcastle Disease Virus Isolated from Laying Ducks in Jiangsu, China

    PubMed Central

    Liu, Mei; Shen, Xinyue; Cheng, Xu; Li, Jianmei

    2015-01-01

    We report here the complete genome sequence and biological characterization of a virulent Newcastle disease virus (NDV) strain, NDV/duck/Jiangsu/JSD0812/2008, isolated from laying ducks in Jiangsu Province, China. The genome is 15,192 nucleotides in length and is classified in subgenotype VIId of genotype VII, class II. PMID:26634760

  14. Characterization and Sequencing of a Genotype VIId Newcastle Disease Virus Isolated from Laying Ducks in Jiangsu, China.

    PubMed

    Liu, Mei; Shen, Xinyue; Cheng, Xu; Li, Jianmei; Dai, Yabin

    2015-01-01

    We report here the complete genome sequence and biological characterization of a virulent Newcastle disease virus (NDV) strain, NDV/duck/Jiangsu/JSD0812/2008, isolated from laying ducks in Jiangsu Province, China. The genome is 15,192 nucleotides in length and is classified in subgenotype VIId of genotype VII, class II. PMID:26634760

  15. Influenza-A viruses in ducks in northwestern Minnesota: fine scale spatial and temporal variation in prevalence and subtype diversity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Waterfowl from northwestern Minnesota were sampled by cloacal swabbing for Avian Influenza Virus (AIV) from July – October in 2007 and 2008. AIV was detected in 222 (9.1%) of 2,441 ducks in 2007 and in 438 (17.9%) of 2,452 ducks in 2008. Prevalence of AIV peaked in late summer. We detected 27 A...

  16. Genetic characterization and evolutionary analysis of Newcastle disease virus isolated from domestic duck in South Korea.

    PubMed

    Gaikwad, Satish; Kim, Ji-Ye; Lee, Hyun-Jeong; Jung, Suk Chan; Choi, Kang-Seuk

    2016-03-15

    Domestic ducks are considered a potential reservoir of Newcastle disease virus. In the study, a Newcastle disease virus (NDV) isolated from a domestic duck during surveillance in South Korea was characterized. The complete genome of the NDV isolate was sequenced, and the phylogenetic relationship to reference strains was studied. Phylogenetic analysis revealed that the strain clustered in genotype I of Class II ND viruses, has highly phylogenetic similarity to NDV strains isolated from waterfowl in China, but was distant from the viruses isolated in chickens and vaccine strains used in South Korea. Pathogenicity experiment in chickens revealed it to be a lentogenic virus. The deduced amino acid sequence of the cleavage site of the fusion (F) protein confirmed that the isolate contained the avirulent motif (112)GKQGRL(117) at the cleavage site and caused no apparent disease in chickens and ducks. With phylogeographic analysis based on fusion gene, we estimate the origin of an ancestral virus of the isolate and its sister strain located in China around 1998. It highlights the need of continuous surveillance to enhance current understanding of the molecular epidemiology and evolution of the pathogenic strains. PMID:26721461

  17. [The return of the hepatitis delta virus].

    PubMed

    Zoutendijk, R; de Jonge, P J F; de Man, R A

    2016-01-01

    - There are several regions worldwide with a high prevalence of infection with the hepatitis delta virus (HDV) in hepatitis B virus (HBV) carriers.- Chronic HDV infection is occurring with increasing frequency due to increased immigration.- HDV transmission can take place through the same routes as HBV by simultaneous infection with both viruses (co-infection) or infection of an HBV carrier with HDV (superinfection).- Delta hepatitis is considered as the most severe form of viral hepatitis with a high risk of progression to cirrhosis and hepatocellular carcinoma.- Chronic delta hepatitis is exclusively observed in patients who are HBV carriers.- Pegylated interferon is currently the only registered therapy for patients with delta hepatitis, but leads to a persistent virological response in only a minority of them, and rarely leads to a complete cure.- New antivirals, such as viral entry blockers, prenylation inhibitors and anti-sense oligonucleotides are promising and currently being investigated in phase 2 trials. PMID:27405575

  18. Development of a PCR-Based Reverse Genetics System for an Attenuated Duck Tembusu Virus Strain

    PubMed Central

    Wu, Xiaogang; Shi, Ying; Yan, Dawei; Li, Xuesong; Yan, Pixi; Gao, Xuyuan; Zhang, Yuee; Yu, Lei; Ren, Chaochao; Li, Guoxin; Yan, Liping; Teng, Qiaoyang; Li, Zejun

    2016-01-01

    The infectious disease caused by the duck Tembusu virus (DTMUV) has resulted in massive economic losses to the Chinese duck industry in China since 2010. Research on the molecular basis of DTMUV pathogenicity has been hampered by the lack of a reliable reverse genetics system for this virus. Here we developed a PCR-based reverse genetics system with high fidelity for the attenuated DTMUV strain FX2010-180P. The rescued virus was characterized by using both indirect immunofluorescence assays (IFA) and whole genome sequencing. The rescued virus (rFX2010-180P) grew to similar titers as compared with the wild-type virus in DF-1 cells, and had similar replication and immunogenicity properties in ducks. To determine whether exogenous proteins could be expressed from DTMUV, both an internal ribosomal entry site (IRES) and the enhanced green fluorescent protein (eGFP) gene were introduced between the NS5 gene and the 3' non-coding sequence of FX2010-180P. A recombinant DTMUV expressing eGFP was rescued, but eGFP expression was unstable after 4 passages in DF-1 cells due to a deletion of 1,294 nucleotides. The establishment of a reliable reverse genetics system for FX2010-180P provides a foundation for future studies of DTMUV. PMID:27248497

  19. Study of the early steps of the Hepatitis B Virus life cycle

    PubMed Central

    2004-01-01

    Hepatitis B virus (HBV) is a human pathogen, causing the serious liver disease. Despite considerable advances in the understanding of the natural history of HBV disease, most of the early steps in the virus life cycle remain unclear. Virus attachment to permissive cells, fusion and penetration through cell membranes and subsequent genome release, are largely a mystery. Current knowledge on the early steps of HBV life cycle has mostly come from molecular cloning, expression of individual genes and studies of the infection of duck hepatitis B virus (DHBV) with duck primary duck hepatocytes. However, considering of the difference of the surface protein of HBV and DHBV both in the composition and sequence, the degree to which information from DHBV applies to human HBV attachment and entry may be limited. A major obstacle to the study HBV infection is the lack of a reliable and sensitive in vitro infection system. We have found that the digestion of HBV and woodchuck hepatitis virus (WHBV) by protease V8 led to the infection of HepG2 cell, a cell line generally is refractory for their infection [Lu et al. J Virol. 1996. 70. 2277-2285 . Lu et al. Virus Research. 2001. 73(1): 27-4].. Further studies showed that a serine protease inhibitor Kazal (SPIK) was over expressed in the HepG2 cells. Therefore, it is possible that to silence the over expressed SPIK and thus to reinstate the activity of indispensable cellular proteases can result in the restoration of the susceptibility of HepG2 cells for HBV infection. The establishing a stable cell line for study of the early steps of HBV life cycle by silencing of SPIK is discussed. PMID:15912187

  20. Differences in pathogenicity and response to vaccination between Pekin and Muscovy ducks infected with H5N1 highly pathogenic influenza viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ducks have been implicated in the dissemination and evolution of H5N1 highly pathogenic avian influenza (HPAI) viruses. Vaccination of domestic ducks against H5N1 HPAI is being conducted as a method of control but with mixed results. One of the observations from the field is that Muscovy ducks (Cair...

  1. Structural, Antigenic, and Evolutionary Characterizations of the Envelope Protein of Newly Emerging Duck Tembusu Virus

    PubMed Central

    Huang, Bing; Ma, Xiuli; Li, Yufeng; Yuan, Xiaoyuan; Qin, Zhuoming; Wang, Dan; Chakravarty, Suvobrata; Li, Feng; Song, Minxun; Sun, Huaichang

    2013-01-01

    Since the first reported cases of ducks infected with a previously unknown flavivirus in eastern China in April 2010, the virus, provisionally designated Duck Tembusu Virus (DTMUV), has spread widely in domestic ducks in China and caused significant economic losses to poultry industry. In this study, we examined in detail structural, antigenic, and evolutionary properties of envelope (E) proteins of six DTMUV isolates spanning 2010–2012, each being isolated from individual farms with different geographical locations where disease outbreaks were documented. Structural analysis showed that E proteins of DTMUV and its closely related flavivirus (Japanese Encephalitis Virus) shared a conserved array of predicted functional domains and motifs. Among the six DTMUV strains, mutations were observed only at thirteen amino acid positions across three separate domains of the E protein. Interestingly, these genetic polymorphisms resulted in no detectable change in viral neutralization properties as demonstrated in a serum neutralization assay. Furthermore, phylogenetic analysis of the nucleotide sequences of the E proteins showed that viruses evolved into two distinct genotypes, termed as DTMUV.I and DTMUV.II, with II emerging as the dominant genotype. New findings described here shall give insights into the antigenicity and evolution of this new pathogen and provide guidance for further functional studies of the E protein for which no effective vaccine has yet been developed. PMID:23990944

  2. Dengue causing fulminant hepatitis in a hepatitis B virus carrier.

    PubMed

    Agarwal, M P; Giri, S; Sharma, V; Roy, U; Gharsangi, K

    2011-01-01

    Dengue is an acute febrile illness resulting from infection by a flavivirus transmitted by the Aedes mosquito. It is characterized by bleeding manifestations and a plasma leak syndrome. Hepatic involvement in the form of elevation in transaminases is common. However, acute hepatic failure is uncommon. It is not known how the presence of an underlying chronic hepatitis or liver disease affects the likelihood of severity of hepatitis from dengue. The present report is of a 33-year-old man, a carrier of hepatitis B virus, who presented with fever, altered sensorium, thrombocytopenia, and coagulopathy. He was diagnosed to have developed acute hepatic failure due to dengue. The patient improved with supportive measures. PMID:21422600

  3. Biologic characterization of chicken-derived H6N2 low pathogenic avian influenza viruses in chickens and ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this study we biologically characterized H6N2 low pathogenicity avian influenza (LPAI) viruses by infecting chickens and ducks in order to compare adaptation of these viruses in these species. We examined the clinical signs, virus shedding, and immune response to infection in 4-week old white le...

  4. Hepatitis C Virus in Pregnancy

    PubMed Central

    Prasad, Mona R; Honegger, Jonathan R.

    2013-01-01

    Despite recent advances in the pathogenesis, treatment, and public health response to hepatitis C virus (HCV), HCV as it specifically relates to pregnancy has been a neglected condition and a markedly improved public health response to these populations is needed. HCV-monoinfected pregnant women have a 2–8% risk of viral transmission to their infant, but the mechanism and timing of mother to child transmission (MTCT) are not fully understood, nor is the natural history of the illness in pregnant women and their offspring. Recognition of HCV is relevant to infected pregnant women because of their risk of the long-term complications of infection, potential effects of infection on pregnancy, and risk of transmission to their infants. Certain risk factors for mother to child transmission (MTCT) of HCV appear similar to those for human immunodeficiency virus (HIV), however, unlike HIV, effective methods of prevention of HCV vertical transmission have not been developed. It is possible that a better understanding of HCV pathogenesis in pregnancy and MTCT of HCV infection will lead to useful prevention strategies, particularly as we enter an era where interferon-free drug cocktails may emerge as viable treatment options for HCV PMID:23389935

  5. Hepatitis B Virus X Protein and Hepatocarcinogenesis.

    PubMed

    Liu, Shuaichen; Koh, Samantha S Y; Lee, Caroline G L

    2016-01-01

    Chronic hepatitis B virus (HBV) infection is one of the most associated factors in hepatocarcinogenesis. HBV is able to integrate into the host genome and encode the multi-functional hepatitis B virus x protein (HBx). Although the mechanism between HBx and carcinogenesis is still elusive, recent studies have shown that HBx was able to influence various signaling pathways, as well as epigenetic and genetic processes. This review will examine and summarize recent literature about HBx's role in these various processes. PMID:27314335

  6. Novel Reassortant Influenza A(H5N8) Viruses among Inoculated Domestic and Wild Ducks, South Korea, 2014

    PubMed Central

    Kang, Hyun-Mi; Lee, Eun-Kyoung; Song, Byung-Min; Jeong, Jipseol; Choi, Jun-Gu; Jeong, Joojin; Moon, Oun-Kyong; Yoon, Hachung; Cho, Youngmi; Kang, Young-Myong; Lee, Hee-Soo

    2015-01-01

    An outbreak of highly pathogenic avian influenza, caused by a novel reassortant influenza A (H5N8) virus, occurred among poultry and wild birds in South Korea in 2014. The aim of this study was to evaluate the pathogenesis in and mode of transmission of this virus among domestic and wild ducks. Three of the viruses had similar pathogenicity among infected domestic ducks: the H5N8 viruses were moderately pathogenic (0%–20% mortality rate); in wild mallard ducks, the H5N8 and H5N1 viruses did not cause severe illness or death; viral replication and shedding were greater in H5N8-infected mallards than in H5N1-infected mallards. Identification of H5N8 viruses in birds exposed to infected domestic ducks and mallards indicated that the viruses could spread by contact. We propose active surveillance to support prevention of the spread of this virus among wild birds and poultry, especially domestic ducks. PMID:25625281

  7. From DCPD to NTCP: The long journey towards identifying a functional hepatitis B virus receptor

    PubMed Central

    2015-01-01

    Hepatitis B virus (HBV) is the prototype of hepatotropic DNA viruses (hepadnaviruses) infecting a wide range of human and non-human hosts. Previous studies with duck hepatitis B virus (DHBV) identified duck carboxypeptidase D (dCPD) as a host specific binding partner for full-length large envelope protein, and p120 as a binding partner for several truncated versions of the large envelope protein. p120 is the P protein of duck glycine decarboxylase (dGLDC) with restricted expression in DHBV infectible tissues. Several lines of evidence suggest the importance of dCPD, and especially p120, in productive DHBV infection, although neither dCPD nor p120 cDNA could confer susceptibility to DHBV infection in any cell line. Recently, sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a binding partner for the N-terminus of HBV large envelope protein. Importantly, knock down and reconstitution experiments unequivocally demonstrated that NTCP is both necessary and sufficient for in vitro infection by HBV and hepatitis delta virus (HDV), an RNA virus using HBV envelope proteins for its transmission. What remains unclear is whether NTCP is the major HBV receptor in vivo. The fact that some HBV patients are homozygous with an NTCP mutation known to abolish its receptor function suggests the existence of NTCP-independent pathways of HBV entry. Also, NTCP very likely mediates just one step of the HBV entry process, with additional co-factors for productive HBV infection still to be discovered. NTCP offers a novel therapeutic target for the control of chronic HBV infection. PMID:26523264

  8. Host Innate Immune Responses of Ducks Infected with Newcastle Disease Viruses of Different Pathogenicities

    PubMed Central

    Kang, Yinfeng; Li, Yanling; Yuan, Runyu; Feng, Minsha; Xiang, Bin; Sun, Minhua; Li, Yaling; Xie, Peng; Tan, Yangtong; Ren, Tao

    2015-01-01

    Though previous studies have identified two strains of duck-origin Newcastle disease virus (NDV) with varying levels of pathogenicity, the relationship between the early-phase host innate immune response, and pathogenesis of ducks infected with these strains in the lungs and thymuses remains unclear. In this study, we compared the viral distribution and mRNA expression of immune-related genes in ducks following infection with two NDV strains, Duck/CH/GD/SS/10 (SS-10) and Duck/CH/GD/NH/10 (NH-10). Both NDV strains replicated systemically in tested tissues (i.e., small intestine, cecal tonsils, brain, lung, bursa of Fabricius, thymus, and spleen) and exhibited different biological properties in duck pathogenicity. Real-time quantitative polymerase chain reaction showed that the expression of TLR3, TLR7, RIG-I, MDA5, IL-1β, IL-2, IL-6, IL-8, IFN-alpha, IFN-beta, IFN-gamma in the lungs was significantly greater than in the respective thymus genes during the early post infection stage. However, in the lungs, the expression of TLR3, TLR7, IL-1β, IL-2, IL-8, IFN-alpha, IFN-gamma, and MHC II induced by SS-10 at 72 h post-inoculation (hpi) was less than with NH-10. Furthermore, the expression of IL-6 and IFN-beta in the lungs and thymuses following infection with SS-10 was greater than that with NH-10 at 24 and 48 hpi. These results highlight important differences in host innate immune responses, courses of infection, and pathogenesis following NDV infection. Further studies should work to expand understandings of the molecular mechanisms related to NDV infection. PMID:26635752

  9. Complete Genome Sequence of Avian Tembusu-Related Virus Strain WR Isolated from White Kaiya Ducks in Fujian, China

    PubMed Central

    Wan, Chunhe; Fu, Guanghua; Shi, Shaohua; Cheng, Longfei; Chen, Hongmei

    2012-01-01

    Avian tembusu-related virus, which was first identified in China, is an emerging virus causing serious economic loss to the Chinese poultry industry. We report here the complete genome sequences of avian tembusu-related virus strain WR, isolated from a White Kaiya duck with disease characterized by an abrupt decrease in egg laying with ovarian hemorrhage, which will help in further understanding the molecular and evolutionary characteristics and pathogenesis of avian tembusu-related virus, the new flavivirus affecting ducks in Southern China. PMID:22966199

  10. Chronic Hepatitis E Virus Infection and Treatment

    PubMed Central

    Kamar, Nassim; Izopet, Jacques; Dalton, Harry R.

    2013-01-01

    It is now well accepted that hepatitis E virus (HEV) infection can induce chronic hepatitis and cirrhosis in immunosuppressed patients. Chronic genotype-3 HEV infections were first reported in patients with a solid-organ transplant. Thereafter, cases of chronic HEV infection have been reported in patients with hematological disease and in those who are human immunodeficiency virus (HIV)-positive. HEV-associated extra-hepatic manifestations, including neurological symptoms, kidney injuries, and hematological disorders, have been also reported. In transplant patients, reducing the dosage of immunosuppressive drugs allows the virus to be cleared in some patients. In the remaining patients, as well as hematological patients and patients who are HIV-positive, anti-viral therapies, such as pegylated interferon and ribavirin, have been found to be efficient in eradicating HEV infection. This review summarizes our current knowledge of chronic HEV infection, its treatment, and the extra-hepatic manifestations induced by HEV. PMID:25755487

  11. Pathobiological characterization of low-pathogenicity H5 avian influenza viruses of diverse origins in chickens, ducks and turkeys.

    PubMed

    Pillai, S P S; Pantin-Jackwood, M; Suarez, D L; Saif, Y M; Lee, C-W

    2010-09-01

    We undertook one of the most comprehensive studies on the replication and intraspecies transmission characteristics of low-pathogenicity avian influenza viruses in ducks, chickens and turkeys. Our results indicated that most of these isolates could replicate and be transmitted in poultry without inducing clinical disease. However, differences in transmission to contact control birds were noted, emphasizing the importance of having contact control cage mates in biological characterization experiments. Ducks supported the replication of viruses of wild aquatic bird origin in their respiratory and digestive tracts equally well. The viruses from wild aquatic birds were not effectively transmitted among chickens. In contrast, the wild-bird isolates and viruses of domestic bird origin from live-bird markets and commercial poultry operations replicated and were transmitted more efficiently in turkeys than in chickens or ducks. We also found a lower minimal infectious dose requirement for infection of turkeys compared to chickens and ducks. Our data support an important role of turkeys as being more susceptible hosts for avian influenza viruses than domestic ducks and chickens. These results highlight the role of turkeys as intermediate or bridging hosts in the transmission of influenza viruses from wild birds to land-based domestic poultry or among different land-based bird species. PMID:20577770

  12. Hepatitis C Virus Exploitation of Processing Bodies.

    PubMed

    Biegel, Jason M; Pager, Cara T

    2016-05-15

    During infection, positive-strand RNA viruses subvert cellular machinery involved in RNA metabolism to translate viral proteins and replicate viral genomes to avoid or disable the host defense mechanisms. Cytoplasmic RNA granules modulate the stabilities of cellular and viral RNAs. Understanding how hepatitis C virus and other flaviviruses interact with the host machinery required for protein synthesis, localization, and degradation of mRNAs is important for elucidating how these processes occur in both virus-infected and uninfected cells. PMID:26937026

  13. Complete Genome Sequence of a Genotype XVII Newcastle Disease Virus, Isolated from an Apparently Healthy Domestic Duck in Nigeria.

    PubMed

    Shittu, Ismaila; Sharma, Poonam; Joannis, Tony M; Volkening, Jeremy D; Odaibo, Georgina N; Olaleye, David O; Williams-Coplin, Dawn; Solomon, Ponman; Abolnik, Celia; Miller, Patti J; Dimitrov, Kiril M; Afonso, Claudio L

    2016-01-01

    The first complete genome sequence of a strain of Newcastle disease virus (NDV) of genotype XVII is described here. A velogenic strain (duck/Nigeria/903/KUDU-113/1992) was isolated from an apparently healthy free-roaming domestic duck sampled in Kuru, Nigeria, in 1992. Phylogenetic analysis of the fusion protein gene and complete genome classified the isolate as a member of NDV class II, genotype XVII. PMID:26847901

  14. Complete Genome Sequence of a Genotype XVII Newcastle Disease Virus, Isolated from an Apparently Healthy Domestic Duck in Nigeria

    PubMed Central

    Shittu, Ismaila; Sharma, Poonam; Joannis, Tony M.; Volkening, Jeremy D.; Odaibo, Georgina N.; Olaleye, David O.; Williams-Coplin, Dawn; Solomon, Ponman; Abolnik, Celia; Miller, Patti J.; Dimitrov, Kiril M.

    2016-01-01

    The first complete genome sequence of a strain of Newcastle disease virus (NDV) of genotype XVII is described here. A velogenic strain (duck/Nigeria/903/KUDU-113/1992) was isolated from an apparently healthy free-roaming domestic duck sampled in Kuru, Nigeria, in 1992. Phylogenetic analysis of the fusion protein gene and complete genome classified the isolate as a member of NDV class II, genotype XVII. PMID:26847901

  15. Identification and molecular characterization of a novel duck Tembusu virus isolate from Southwest China.

    PubMed

    Zhu, Kesen; Huang, Juan; Jia, Renyong; Zhang, Bin; Wang, Mingshu; Zhu, Dekang; Chen, Shun; Liu, Mafeng; Yin, Zhongqiong; Cheng, Anchun

    2015-11-01

    Tembusu virus (TMUV) has caused significant economic losses in the Chinese duck industry and may have been overlooked regarding its zoonotic transmission potential. A novel TMUV isolate (named CQW1) was separated from the liver tissue of a young duck in Southwest China. The CQW1 isolate proliferated in embryonated duck eggs and led to death within 3-4 days post-inoculation. Furthermore, CQW1 replicated in duck embryo fibroblast (DEF) cells and caused a cytopathic effect (CPE). The disease emerged on a duck farm in Southwest China and was reproduced by animal experiment. We found that CQW1 was detectable by RT-PCR in brain and liver tissues of dead ducklings within 5 days after inoculation. Most importantly, concentrated nuclei, neuronophagia and microglial nodules were observed in the brain tissue of the inoculated ducklings, and additionally, the liver tissue was affected, mainly by disordered lobular architecture, degeneration, necrosis and regenerated hepatocytes. Analysis of the complete genome sequence showed that CQW1 was 10,992 nt in length with two nucleotide insertions and shared 96.8% to 99.1% and 98.4% to 99.6% identity at nucleotide and amino acid level, respectively, with Chinese isolates. Phylogenetic analysis of the nucleotide sequences demonstrated that the CQW1 isolate was closely related to other members of the genus Flavivirus and formed a new clade together with the GX2013H isolate. Also, the CQW1 isolate demonstrated the highest average pairwise distance value among the Chinese isolates. In the present study, we obtained evidence that TMUV is present in Southwest China. Extensive pathological and epidemiological studies are urgently needed. PMID:26303137

  16. [The Isolation and Identification of Infectious Bronchitis Virus PTFY Strain in Muscovy Ducks].

    PubMed

    Wu, Xiaoping; Pan, Shulei; Zhou, Wuduo; Wu, Yijiang; Huang, Yifan; Wu, Baocheng

    2016-03-01

    In July 2009, some farms of breeding Muscovy ducks on the peak of egg laying suffered the decrease of hatching rate and the quality of the eggs showing low mortality and no evident respiratory symptoms. The swelling and congestive ovary was visible after autopsy. This study was brought out for the diagnosis of these cases. The virus was isolated and identified by the methods of virus culture in chicken embryo, physical and chemical properties test, hemagglutinin test, NDV (Newcastle diseases Virus) interference test, electron microscope observation, pathogenicity test and the gene sequence analysis. The results indicated the virus showed the characters of inducing dwarf embryo after inocubation, the sensibility to lipid solvent and the hemagglutination capacity after pancreatic enzyme treatment, the typical morphology of coronavirus, the interference to NDV replication and the homology among 84.7% - 99% of the particial N gene sequences to the reference IBV (Avian infectious bronchitis virus) strains. The strain was identified as IBV isolate and this study confirmed the pathogenicity of IBV to Muscovy ducks. PMID:27396165

  17. Duck tembusu virus and its envelope protein induce programmed cell death.

    PubMed

    Shaozhou, Wulin; Li, Chenxi; Zhang, Qingshan; Meng, Runzhe; Gao, Youlan; Liu, Hongyu; Bai, Xiaofei; Chen, Yuhuan; Liu, Ming; Liu, Siguo; Zhang, Yun

    2015-08-01

    The cytopathic effect produced in cells infected with duck tembusu virus (DTMUV) suggests that this emerging virus may induce apoptosis in primary cultures of duck embryo fibroblasts (DEF). Here, we present evidence that DTMUV infection of cultured cells activates apoptosis and that the ability of DTMUV to induce apoptosis is not restricted to cell type because DTMUV-induced apoptosis in duck and mammalian host cells. We further investigated which viral components induce apoptosis in DTMUV-infected host cells. The major envelope glycoprotein (E) was investigated for its apoptotic activities in expressed cells. Transient expression of the E protein alone triggered apoptosis in DEF, Vero, and BHK cells. Expression of the E protein resulted in activation of caspase-3-like proteases in cultured cells. These results indicate that infection of cells with DTMUV or expression of DTMUV E protein alone induces apoptosis, providing the basis for future to define the molecules that play key roles in the fate of DTMUV-infected cells. PMID:26056013

  18. Origins and Evolution of Hepatitis B Virus and Hepatitis D Virus.

    PubMed

    Littlejohn, Margaret; Locarnini, Stephen; Yuen, Lilly

    2016-01-01

    Members of the family Hepadnaviridae fall into two subgroups: mammalian and avian. The detection of endogenous avian hepadnavirus DNA integrated into the genomes of zebra finches has revealed a deep evolutionary origin of hepadnaviruses that was not previously recognized, dating back at least 40 million and possibly >80 million years ago. The nonprimate mammalian members of the Hepadnaviridae include the woodchuck hepatitis virus (WHV), the ground squirrel hepatitis virus, and arctic squirrel hepatitis virus, as well as a number of members of the recently described bat hepatitis virus. The identification of hepatitis B viruses (HBVs) in higher primates, such as chimpanzee, gorilla, orangutan, and gibbons that cluster with the human HBV, as well as a number of recombinant forms between humans and primates, further implies a more complex origin of this virus. We discuss the current theories of the origin and evolution of HBV and propose a model that includes cross-species transmissions and subsequent recombination events on a genetic backbone of genotype C HBV infection. The hepatitis delta virus (HDV) is a defective RNA virus requiring the presence of the HBV for the completion of its life cycle. The origins of this virus remain unknown, although some recent studies have suggested an ancient African radiation. The age of the association between HDV and HBV is also unknown. PMID:26729756

  19. Age at infection affects the pathogenicity of Asian highly pathogenic avian influenza H5N1 viruses in ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Asian H5N1 avian influenza (AI) viruses have changed from producing no disease or mild respiratory infections in ducks to some strains causing systemic disease and death. Differences in pathogenicity between four of these viruses as well as the effect of host age on the outcome of infection were...

  20. Evaluation of hepatocyteprotective and anti-hepatitis B virus properties of Cichoric acid from Cichorium intybus leaves in cell culture.

    PubMed

    Zhang, Hong-Li; Dai, Ling-Hao; Wu, Yi-Hang; Yu, Xiao-Ping; Zhang, Yong-Yong; Guan, Rong-Fa; Liu, Tao; Zhao, Jun

    2014-01-01

    Hepatitis B is the most common serious liver infection in the world. To date, there is still no complete cure for chronic hepatitis B. Natural caffeic acid analogues possess prominent antiviral activity, especially anti-hepatitis B virus (HBV) and anti-human immunodeficiency virus effects. Cichoric acid is a caffeic acid derivative from Cichorium intybus. In the study, the anti-hepatitis B property of cichoric acid was evaluated by the D-galactosamine (D-GalN)-induced normal human HL-7702 hepatocyte injury model, the duck hepatitis B virus (DHBV)-infected duck fetal hepatocytes and the HBV-transfected cell line HepG2.2.15 cells, respectively. The results showed that cichoric acid attenuated significantly D-GalN-induced HL-7702 hepatocyte injury at 10-100 µg/mL and produced a maximum protection rate of 56.26%. Moreover, cichoric acid at 1-100 µg/mL inhibited markedly DHBV DNA replication in infected duck fetal hepatocytes. Also, cichoric acid at 10-100 µg/mL reduced significantly the hepatitis B surface and envelope antigen levels in HepG2.2.15 cells and produced the maximum inhibition rates of 79.94% and 76.41%, respectively. Meanwhile, test compound at 50-100 µg/mL inhibited markedly HBV DNA replication. In conclusion, this study verifies the anti-hepatitis B effect of cichoric acid from Cichorium intybus leaves. In addition, cichoric acid could be used to design the antiviral agents. PMID:24759764

  1. Effects of petroleum on adrenocortical activity and on hepatic naphthalene-metabolizing activity in mallard ducks

    USGS Publications Warehouse

    Gorsline, J.; Holmes, W.N.

    1981-01-01

    Unstressed mallard ducks (Anas platyrhychos), given uncontaminated food and maintained on a short photoperiod, show two daily maxima in plasma corticosterone concentration ([B]); one occurring early in the light phase and a second just before the onset of darkness. After one week of exposure to food containing 3% (v/w) South Louisiana crude oil, plasma [B] were significantly lowered throughout the day. Similar abrupt declines in plasma [B] also occurred during the first 10 days of exposure to food containing 1% and 0.5% crude oil. Although the plasma [B] in birds consuming food contaminated with 0.5% crude oil increased between 10 and 50 days of exposure, the concentration after 50 days was still lower than normal. During the same interval, normal plasma [B] were restored in birds consuming food containing 1% and 3% crude oil. Significant increases occurred in the naphthalene-metabolizing properties of hepatic microsomes prepared from birds acutely exposed to all levels of petroleum-contaminated food and elevated levels were sustained throughout the first 50 days of exposure. Birds given food containing 3% crude oil for more than 50 days, however, showed steady declines in hepatic naphthalene-metabolizing activity. After 500 days, the activity was similar to that found in contemporaneous controls. During the same interval, the plasma [B] increased until the levels were higher than normal after 500 days of exposure; at this time, an inverse relationship, similar to that seen during the first week of exposure to contaminated food, was once more established between plasma [B] and the concomitant hepatic naphthalene-metabolizing activity.

  2. Complete Genome Sequence of a Virulent Newcastle Disease Virus Strain Isolated from a Clinically Healthy Duck (Anas platyrhynchos domesticus) in Pakistan

    PubMed Central

    Wajid, Abdul; Rehmani, Shafqat F.; Wasim, Muhammad; Basharat, Asma; Bibi, Tasra; Arif, Saima; Dimitrov, Kiril M.

    2016-01-01

    Here, we report the complete genome sequence of a virulent Newcastle disease virus (vNDV) strain, duck/Pakistan/Lahore/AW-123/2015, isolated from apparently healthy laying ducks (Anas platyrhynchos domesticus) from the province of Punjab, Pakistan. The virus has a genome length of 15,192 nucleotides and is classified as member of subgenotype VIIi, class II. PMID:27469959

  3. Complete Genome Sequence of a Virulent Newcastle Disease Virus Strain Isolated from a Clinically Healthy Duck (Anas platyrhynchos domesticus) in Pakistan.

    PubMed

    Wajid, Abdul; Rehmani, Shafqat F; Wasim, Muhammad; Basharat, Asma; Bibi, Tasra; Arif, Saima; Dimitrov, Kiril M; Afonso, Claudio L

    2016-01-01

    Here, we report the complete genome sequence of a virulent Newcastle disease virus (vNDV) strain, duck/Pakistan/Lahore/AW-123/2015, isolated from apparently healthy laying ducks (Anas platyrhynchos domesticus) from the province of Punjab, Pakistan. The virus has a genome length of 15,192 nucleotides and is classified as member of subgenotype VIIi, class II. PMID:27469959

  4. Isolation of a novel serotype strain of infectious bronchitis virus ZZ2004 from ducks in China.

    PubMed

    Yao, Sixin; Ou, Changbo; Liu, Xingyou; Wang, Xianwen; Yao, Zonghui; Liu, Jinjing

    2016-10-01

    In chickens, the infectious bronchitis virus (IBV) often causes respiratory distress, a decrease in egg production, poor egg quality, and occasional nephritis. However, ZZ2004, a Chinese isolate of IBV, was obtained from ducks with clinical growth suppression and mild respiratory symptoms that had been reared with chickens in the central region of China. Virus isolation, virus neutralization testing, and RT-PCR were employed to identify the causative pathogen, while sequence alignment was used to analyze gene variations of the S1 subunit and M genes. The results showed that the ducks were infected with IBV due to the emergence of a dwarfing phenotype and the death of embryos between 48 and 144 h post-inoculation. RT-PCR also confirmed the presence of the expected fragment sizes of the S1 subunit and M genes by RT-PCR. Meanwhile, the results of the virus neutralization test indicated that the strains of JX/99/01, GD, SAIBK, LDT3 showed cross-reactivity with the ZZ2004 isolate, and hardly any cross-neutralization of IBV ZZ2004 was observed with the strains of M41, H120, Gray, Holte, or Aust-T. Phylogenetic analysis suggested that there were large differences between ZZ2004 and other IBV reference strains on the S1 subunit. Meanwhile, homologies in the nucleotide and amino acid sequences of the M gene of IBV ZZ2004 were 86.9-92.0 % and 91.1-93.9 %, respectively, compared with 35 other IBV reference strains derived from different regions. This result revealed that there were conspicuous variations among the selected strains. Furthermore, the results showed that the prevalent strains of IBV in ducks had no antigen homology with the vaccine strains widely used in China except the LDT3-strain, making it urgent to explore and develop new IBV vaccines. PMID:27164844

  5. Genomic Characterizations of a Newcastle Disease Virus Isolated from Ducks in Live Bird Markets in China

    PubMed Central

    Zhang, Yi; Zheng, Dongxia; Zhao, Yunling; Castellan, David; Liu, Hualei; Wang, Zhiliang

    2016-01-01

    One class I Newcastle disease virus (NDV), designated as duck/Guangxi/1261/2015 (GX1261), was isolated from asymptomatic ducks in live bird markets (LBM) from southern China during the national active surveillance for NDVs in 2015. The complete genome length of GX1261 isolate was 15,198 nucleotides with the gene order of 3’-NP-P-M-F-HN-L-5’. The motif at the cleavage site of F protein was 112ERQER/L117, which was typical of low virulence NDV. Several mutations were identified in the functional domains of F and HN proteins, including fusion peptide, heptad repeat region, transmembrane domains and neutralizing epitopes. Phylogenetic analysis based on the complete F gene revealed that the isolate was clustered into sub-genotype 1c in class I, and showed a high level of similarity with the strains isolated from waterfowl in the United States of America. This is the first report of this kind of virus in the mainland of China. These results demonstrated that GX1261-like viruses might exist in asymptomatic waterfowl, and remain undetected or unidentified. Thus, more investigation needs to be done in order to identify the source of the virus. This study revealed the genetic and phylogenetic characteristics of GX1261 isolate and could help us to better understand the epidemiological context of class I NDV in China. PMID:27391305

  6. Genomic Characterizations of a Newcastle Disease Virus Isolated from Ducks in Live Bird Markets in China.

    PubMed

    Wang, Jingjing; Lv, Yan; Zhang, Yi; Zheng, Dongxia; Zhao, Yunling; Castellan, David; Liu, Hualei; Wang, Zhiliang

    2016-01-01

    One class I Newcastle disease virus (NDV), designated as duck/Guangxi/1261/2015 (GX1261), was isolated from asymptomatic ducks in live bird markets (LBM) from southern China during the national active surveillance for NDVs in 2015. The complete genome length of GX1261 isolate was 15,198 nucleotides with the gene order of 3'-NP-P-M-F-HN-L-5'. The motif at the cleavage site of F protein was 112ERQER/L117, which was typical of low virulence NDV. Several mutations were identified in the functional domains of F and HN proteins, including fusion peptide, heptad repeat region, transmembrane domains and neutralizing epitopes. Phylogenetic analysis based on the complete F gene revealed that the isolate was clustered into sub-genotype 1c in class I, and showed a high level of similarity with the strains isolated from waterfowl in the United States of America. This is the first report of this kind of virus in the mainland of China. These results demonstrated that GX1261-like viruses might exist in asymptomatic waterfowl, and remain undetected or unidentified. Thus, more investigation needs to be done in order to identify the source of the virus. This study revealed the genetic and phylogenetic characteristics of GX1261 isolate and could help us to better understand the epidemiological context of class I NDV in China. PMID:27391305

  7. Hepatitis B Virus X Protein and Hepatocarcinogenesis

    PubMed Central

    Liu, Shuaichen; Koh, Samantha S. Y.; Lee, Caroline G. L.

    2016-01-01

    Chronic hepatitis B virus (HBV) infection is one of the most associated factors in hepatocarcinogenesis. HBV is able to integrate into the host genome and encode the multi-functional hepatitis B virus x protein (HBx). Although the mechanism between HBx and carcinogenesis is still elusive, recent studies have shown that HBx was able to influence various signaling pathways, as well as epigenetic and genetic processes. This review will examine and summarize recent literature about HBx’s role in these various processes. PMID:27314335

  8. Acute hepatitis associated with autochthonous hepatitis E virus infection--San Antonio, Texas, 2009.

    PubMed

    Tohme, Rania A; Drobeniuc, Jan; Sanchez, Roger; Heseltine, Gary; Alsip, Bryan; Kamili, Saleem; Hu, Dale J; Guerra, Fernando; Teshale, Eyasu H

    2011-10-01

    Locally acquired hepatitis E infection is increasingly being observed in industrialized countries. We report 2 cases of autochthonous acute hepatitis E in the United States. Hepatitis E virus genotype 3a related to US-2 and swine hepatitis E virus strains was isolated from one of the patients, indicating potential food-borne or zoonotic transmission. PMID:21896699

  9. Hepatitis B and hepatitis delta virus infection in South America.

    PubMed Central

    Torres, J R

    1996-01-01

    About 100,000 cases of acute hepatitis B virus (HBV) infection occur annually in South America. The overall prevalence of HBV infection in low risk populations ranges from 6.7% to 41%, while hepatitis B surface antigen (HBsAg) rates range from 0.4% to 13%. In high endemicity aboriginal or rural populations, perinatal transmission may play a major part in the spread of HBV. In urban populations, however, horizontal transmission, probably by sexual contact, is the predominant mode of spread, with higher rates of HBV positivity in lower socioeconomic groups. High risk populations such as health care workers and haemodialysis patients show higher rates of HBV infection than comparable populations elsewhere. The risk of posttransfusion hepatitis B remains high in some areas. Concomitant HBV infection may accelerate the chronic liver disease seen in decompensated hepatosplenic schistosomiasis. In the north, the prevalence of hepatitis delta virus (HDV) infection ranks among the highest in the world. In the south, the problem appears negligible although it is increasing within high risk urban communities. HDV superinfection has been the cause of large outbreaks of fulminant hepatitis. The cost of comprehensive or mass vaccination programmes remains unaffordable for most South American countries. Less expensive alternatives such as low dose intradermal schedules of immunisation have been used with success in selected adult subjects. PMID:8786054

  10. Nucleotide sequence of a cloned woodchuck hepatitis virus genome: comparison with the hepatitis B virus sequence.

    PubMed Central

    Galibert, F; Chen, T N; Mandart, E

    1982-01-01

    The complete nucleotide sequence of a woodchuck hepatitis virus genome cloned in Escherichia coli was determined by the method of Maxam and Gilbert. This sequence was found to be 3,308 nucleotides long. Potential ATG initiator triplets and nonsense codons were identified and used to locate regions with a substantial coding capacity. A striking similarity was observed between the organization of human hepatitis B virus and woodchuck hepatitis virus. Nucleotide sequences of these open regions in the woodchuck virus were compared with corresponding regions present in hepatitis B virus. This allowed the location of four viral genes on the L strand and indicated the absence of protein coded by the S strand. Evolution rates of the various parts of the genome as well as of the four different proteins coded by hepatitis B virus and woodchuck hepatitis virus were compared. These results indicated that: (i) the core protein has evolved slightly less rapidly than the other proteins; and (ii) when a region of DNA codes for two different proteins, there is less freedom for the DNA to evolve and, moreover, one of the proteins can evolve more rapidly than the other. A hairpin structure, very well conserved in the two genomes, was located in the only region devoid of coding function, suggesting the location of the origin of replication of the viral DNA. Images PMID:7086958

  11. Chromatographic removal and heat inactivation of hepatitis B virus during the manufacture of human albumin.

    PubMed

    Adcock, W L; MacGregor, A; Davies, J R; Hattarki, M; Anderson, D A; Goss, N H

    1998-10-01

    The purpose of the present study was to examine the efficacy of the chromatographic and pasteurization steps, employed in the manufacture of human albumin, in the removal and/or inactivation of hepatitis B virus (HBV). Most human albumins manufactured today are prepared from donor plasma by fractionation methods that use precipitation with cold ethanol. CSL Limited, an Australian biopharmaceutical company, has recently converted its method of manufacture for albumin from a traditional Cohn fractionation method to a method employing chromatographic techniques. A step-by-step validation of virus removal and inactivation was performed on this manufacturing process, which includes a DEAE-Sepharose(R) and CM-Sepharose(R) Fast Flow ion-exchange step, a Sephacryl(R) S200 High-Resolution gel-filtration step and a bulk pasteurization step where product is held at 60 degreesC for 10 h. HBV partitioning experiments were conducted on scaled-down chromatographic columns with hepatitis B surface antigen (HBsAg) as a marker, whereas the HBV model virus, duck HBV, was used to study the inactivation kinetics during pasteurization. Reductions for HBsAg through the three chromatographic steps resulted in a total log10 decrease of 1.5 log10, whereas more than 6.5 log10 decrease in duck HBV in Albumex(R)5 was achieved during pasteurization. PMID:9756468

  12. An Attenuated Duck Plague Virus (DPV) Vaccine Induces both Systemic and Mucosal Immune Responses To Protect Ducks against Virulent DPV Infection

    PubMed Central

    Huang, Juan; Wang, Mingshu; Shu, Bing; Yu, Xia; Zhu, Dekang; Chen, Shun; Yin, Zhongqiong; Chen, Xiaoyue

    2014-01-01

    Duck plague (DP) is a severe disease caused by DP virus (DPV). Control of the disease is recognized as one of the biggest challenges in avian medicine. Vaccination is an efficient way to control DPV, and an attenuated vaccine is the main routine vaccine. The attenuated DPV vaccine strain CHa is a modified live vaccine, but the systemic and mucosal immune responses induced by this vaccine have been poorly understood. In this study, the immunogenicity and efficacy of the vaccine were evaluated after subcutaneous immunization of ducks. CD4+ and CD8+ T cells were counted by flow cytometry, and humoral and mucosal Ig antibodies were analyzed by enzyme-linked immunosorbent assay (ELISA). The results showed that high levels of T cells and Ig antibodies were present postimmunization and that there were more CD4+ T cells than CD8+ T cells. Titers of humoral IgG were higher than those of humoral IgA. Local IgA was found in each sample, whereas local IgG was found only in the spleen, thymus, bursa of Fabricius, harderian gland, liver, bile, and lung. In a protection assay, the attenuated DPV vaccine completely protected ducks against 1,000 50% lethal doses (LD50) of the lethal DPV strain CHv via oral infection. These data suggest that this subcutaneous vaccine elicits sufficient systemic and mucosal immune responses against lethal DPV challenge to be protective in ducks. This study provides broad insights into understanding the immune responses to the attenuated DPV vaccine strain CHa through subcutaneous immunization in ducks. PMID:24451329

  13. The hepatitis delta virus and its infection

    SciTech Connect

    Rizzeto, M.; Gerin, J.L.; Purcell, R.H.

    1987-01-01

    This book contains over 50 papers. Some of the titles are: Structure and Replication of the Genome of Hepatitis Delta Virus; Clinical Significance of HDV RNA in HDV Disease; HBV DNA in Delta Chronic Carriers; Prevalance of HBV-DNA Among Anti-Hd Positive Patients; and Characterization of LKM/sub 1/ and LKM/sub 2/ Antigens.

  14. Replication strategy of human hepatitis B virus

    SciTech Connect

    Will, H.; Reiser, W.; Weimer, T.; Pfaff, E.; Buescher, M.; Sprengel, R.; Cattaneo, R.; Schaller, H.

    1987-03-01

    To study the replication strategy of the human hepatitis B virus, the 5' end of the RNA pregenome and the initiation sites of DNA plus and minus strands have been mapped. The RNA pregenome was found to be terminally redundant by 120 nucleotides; it is initiated within the pre-C region and may also function as mRNA for synthesis of the major core protein and the hepatitis B virus reverse transcriptase. The hepatitis B virus DNA minus strand is initiated within the direct repeat sequence DR1, it contains a terminal redundancy of up to eight nucleotides, and its synthesis does not require any template switch. The DNA plus strand is primed by a short oligoribonucleotide probably derived from the 5' end of the RNA pregenome, and its synthesis is initiated close to the direct repeat sequence DR2. For its elongation to pass the discontinuity in the DNA minus strand an intramolecular template switch occurs using the terminal redundancy of this template. Thus, the route of reverse transcription and DNA replication of hepatitis B viruses is fundamentally different from that of retroviruses.

  15. Current Management of Hepatitis C Virus Infection.

    PubMed

    Mah'moud, Mitchell A

    2016-01-01

    At least 3 million people in the United States are infected with hepatitis C virus (HCV) infection. Unfortunately, 75% of infected individuals remain undiagnosed and untreated, putting them at risk of advanced liver disease. Because the majority of infected individuals are baby boomers, many societies and organizations recommend HCV screening of persons born between 1945 and 1965. PMID:27154887

  16. Hepatitis in skunks caused by the virus of infectious canine hepatitis.

    PubMed

    Karstad, L; Ramsden, R; Berry, T J; Binn, L N

    1975-10-01

    Two cases of acute, fatal, hepatitis occurred in young, striped skunks (Mephitis mephitis) trapped in southern Ontario. Histologically, lesions in the liver were similar to infectious canine hepatitis. A virus was isolated which produced large intranuclear inclusions in dog kidney cell cultures. These inclusions were Feulgen-positive and fluoresced green with acridine orange stain. The skunk hepatitis isolate was identified as the virus of infectious canine hepatitis by virus neutralization tests. PMID:172663

  17. Virology of hepatitis C virus.

    PubMed

    Fang, J W; Chow, V; Lau, J Y

    1997-11-01

    Advances in molecular biology techniques have allowed the cloning of HCV and the characterization of this virus. This article provides a short summary of our current knowledge on the genomic organization of HCV, the implications of its genetic heterogeneous nature, and the probable replication strategy of this virus. PMID:15560054

  18. Neuroinvasive influenza virus A(H5N8) in fattening ducks, Hungary, 2015.

    PubMed

    Bányai, Krisztián; Bistyák, Andrea Tóthné; Thuma, Ákos; Gyuris, Éva; Ursu, Krisztina; Marton, Szilvia; Farkas, Szilvia L; Hortobágyi, Eleonóra; Bacsadi, Árpád; Dán, Ádám

    2016-09-01

    Highly pathogenic avian influenza (HPAI) A virus H5N8 was detected in far east Asian countries during 2014 and emerged in late 2014 in European countries. Hungary reported a HPAI A(H5N8) outbreak during late winter of 2015 at a Pekin duck fattening facility. Epidemiologic monitoring was extended to holdings in neighboring areas and nearby habitats used by wild birds but failed to identify the source of infection. In addition to respiratory symptoms, the affected birds showed lethargy and neuronal signs, including torticollis. Consistent with this finding, influenza A virus antigen was detected in large quantity in the brain. Molecular analysis of the identified strain showed very close genetic relationship (and >99% nucleotide sequence identity) with co-circulating HPAI A(H5N8) strains. A number of unique or rarely detected amino acid changes was detected in the HA (T220I, R512G), the M2 (I39M), the NA (T211I), the NS1 (P85T), and the PB2 (I261V) proteins of the Hungarian strain. Further studies are needed to demonstrate whether any of these mutations can be linked to neuroinvasiveness and neurovirulence in ducks. PMID:27215706

  19. If You Have Chronic Hepatitis B Virus (HBV) Infection

    MedlinePlus

    If you have chronic hepatitis B virus (HBV) infection . . . If you have chronic hepatitis B virus (HBV) infection, you are not alone. Today, approximately one ... receive pneumococcal polysaccharide vac- cine.  Get vaccinated against hepatitis A. Hepati- tis A can further damage your ...

  20. Infectious vaccinia virus recombinants that express hepatitis B virus surface antigen

    NASA Astrophysics Data System (ADS)

    Smith, Geoffrey L.; Mackett, Michael; Moss, Bernard

    1983-04-01

    Potential live vaccines against hepatitis B virus have been produced. The coding sequence for hepatitis B virus surface antigen (HBsAg) has been inserted into the vaccinia virus genome under control of vaccinia virus early promoters. Cells infected with these vaccinia virus recombinants synthesize and excrete HBsAg and vaccinated rabbits rapidly produce antibodies to HBsAg.

  1. Characterization and Sequencing of an H6N6 Avian Influenza Virus Isolated from Sansui Sheldrake Ducks in Guizhou, Southwestern China.

    PubMed

    Duan, Zhiqiang; Chen, Jiaqi; Ji, Xinqin; Xu, Houqiang; Ruan, Yong; Zhao, Jiafu

    2016-01-01

    Here, we report the complete genome sequence of an H6N6 avian influenza virus (AIV) isolated from Sansui Sheldrake ducks in Guizhou Province, China, in 2014. Phylogenetic analysis showed that the H6N6 virus was a reassortant virus derived from three different H6 subtype lineages. The finding of this study will help us understand the epidemiology and the evolutionary characteristics of H6 subtypes of AIV in ducks in southwestern China. PMID:27174267

  2. Characterization and Sequencing of an H6N6 Avian Influenza Virus Isolated from Sansui Sheldrake Ducks in Guizhou, Southwestern China

    PubMed Central

    Chen, Jiaqi; Ji, Xinqin; Xu, Houqiang; Ruan, Yong; Zhao, Jiafu

    2016-01-01

    Here, we report the complete genome sequence of an H6N6 avian influenza virus (AIV) isolated from Sansui Sheldrake ducks in Guizhou Province, China, in 2014. Phylogenetic analysis showed that the H6N6 virus was a reassortant virus derived from three different H6 subtype lineages. The finding of this study will help us understand the epidemiology and the evolutionary characteristics of H6 subtypes of AIV in ducks in southwestern China. PMID:27174267

  3. Noninvasive Monitoring of Hepatic Damage from Hepatitis C Virus Infection

    PubMed Central

    Alavez-Ramírez, J.; Fuentes-Allen, J. L.; López-Estrada, J.

    2011-01-01

    The mathematical model for the dynamics of the hepatitis C proposed in Avendaño et al. (2002), with four populations (healthy and unhealthy hepatocytes, the viral load of the hepatitis C virus, and T killer cells), is revised. Showing that the reduced model obtained by considering only the first three of these populations, known as basic model, has two possible equilibrium states: the uninfected one where viruses are not present in the individual, and the endemic one where viruses and infected cells are present. A threshold parameter (the basic reproductive virus number) is introduced, and in terms of it, the global stability of both two possible equilibrium states is established. Other central result consists in showing, by model numerical simulations, the feasibility of monitoring liver damage caused by HCV, avoiding unnecessary biopsies and the undesirable related inconveniences/imponderables to the patient; another result gives a mathematical modelling basis to recently developed techniques for the disease assessment based essentially on viral load measurements. PMID:21331263

  4. Infectious bursal disease virus antibodies in eider ducks and Herring Gulls

    USGS Publications Warehouse

    Hollmen, T.; Franson, J.C.; Docherty, D.E.; Kilpi, Mikael; Hario, Martti; Creekmore, L.H.; Petersen, M.R.

    2000-01-01

    We measured antibodies to infectious bursal disease virus (IBDV) in blood of nesting Common Eider (Somateria mollissima) females and immature Herring Gulls (Larus argentatus) in the Baltic Sea, and in blood of Spectacled Eider (Somateria fischeri) females nesting in a remote area of western Alaska. Positive (??? 1:16) IBDV titers occurred in 75% of the eiders and 45% of the Herring Gull chicks. In eiders, the prevalence of positive titers differed among locations. We found no evidence that IBDV exposure impaired the immune function of Herring Gull chicks, based on their response to inoculation of sheep red blood cells. We suggest that eider ducks and Herring Gulls have been exposed to IBDV, even in locations where contact with poultry is unlikely. The presence of this virus in wild bird populations is of concern because it causes mortality of up to 30% in susceptible poultry.

  5. Characterization of nucleocytoplasmic shuttling and intracellular localization signals in Duck Enteritis Virus UL54.

    PubMed

    Liu, Chaoyue; Cheng, Anchun; Wang, Mingshu; Chen, Shun; Jia, Renyong; Zhu, Dekang; Liu, Mafeng; Sun, Kunfeng; Yang, Qiao; Chen, Xiaoyue

    2016-08-01

    Duck Enteritis virus (DEV) UL54 is a homolog of herpes simplex virus-1 (HSV-1) trafficking protein ICP27, which plays an essential role in infection. In this study, DEV UL54 shuttling between the nucleus and cytoplasm was verified with a heterokaryon assay. One predicted nuclear export sequence (NES) (339-348 aa) was shown to be functional and chromosomal region maintenance 1 (CRM1)-dependent; however, the insensitivity of UL54 to Leptomycin B (LMB) and NES mutation suggests that other mechanisms are responsible for the observed nuclear export. Next, three non-classical nuclear localization sequences (NLSs), referred to as NLS1 (105-122 aa), NLS2 (169-192 aa) and NLS3 (257-274 aa), were identified. Furthermore, a recombinant DEV with the UL54 NLSs deleted (DEV- UL54 mNLSs) was constructed and showed that UL54 NLSs moderately affected DEV growth. PMID:27157269

  6. Isolation of avian pneumovirus from mallard ducks that is genetically similar to viruses isolated from neighboring commercial turkeys.

    PubMed

    Shin, Hyun-Jin; Nagaraja, Kakambi V; McComb, Brian; Halvorson, David A; Jirjis, Faris F; Shaw, Daniel P; Seal, Bruce S; Njenga, M Kariuki

    2002-02-26

    Our earlier studies demonstrating avian pneumovirus (APV) RNA in wild geese, sparrows, swallows, starlings and mallard ducks suggested that wild birds might be involved in the circulation of APV in the United States. To determine whether turkey virus can be transmitted to the free flying birds, we placed APV-negative mallard ducks next to a turkey farm experiencing a severe APV outbreak and in an area with a large population of waterfowls. The sentinel ducks did not develop clinical APV disease but infectious APV (APV/MN-12) was recovered from choanal swabs after 2 weeks, and anti-APV antibodies detected after 4 weeks. Four APV isolates recovered from the neighboring turkeys that were experiencing an APV outbreak at the same time shared 95-99% nucleotide identity and 97-99% predicted amino acid identity with the duck isolate. In addition experimental infection of turkey poults with APV/MN-12 resulted in detection of viral RNA in nasal turbinates and APV-specific IgG in serum. These results indicate that the APV isolates from turkeys and ducks shared a common source, and the viruses from different avian species can cross-infect. PMID:11864753

  7. Adaptation and Attenuation of Duck Tembusu Virus Strain Du/CH/LSD/110128 following Serial Passage in Chicken Embryos

    PubMed Central

    Sun, Ling; Li, Yunxia; Zhang, Yue; Han, Zongxi; Xu, Yang

    2014-01-01

    Duck Tembusu virus (DTMUV) is a newly emerging pathogenic flavivirus that has caused massive economic losses to the duck industry in China. In the current study, a virulent strain of DTMUV, designated Du/CH/LSD/110128, was isolated from the livers of diseased ducks and attenuated by serial passage in embryonated chicken eggs. The virus was partially attenuated after 50 and 70 passages and was fully attenuated after 90 passages, based on mortality and morbidity rates and viral loads in inoculated ducklings. Fourteen amino acid substitutions were observed in the capsid, prM, envelope, NS1, NS3, NS4A, NS4B, and NS5 proteins of the fully attenuated strain of Du/CH/LSD/110128, which might be responsible for the observed changes in replication and pathogenicity. A 72-nucleotide deletion was also observed in the 3′ untranslated region of the virus after 30 passages. The fully attenuated virus retained the immunogenicity of the parental strain, providing effective protection to challenge with virulent Du/CH/LSD/110128, and may represent a suitable candidate as a vaccine strain against DTMUV infection in ducks. Our results also lay the foundation for future studies on the replication and pathogenic mechanisms of DTMUV. PMID:24872514

  8. Induced immunity against hepatitis B virus.

    PubMed

    Said, Zeinab Nabil Ahmed; Abdelwahab, Kouka Saadeldin

    2015-06-28

    Prevention of hepatitis B virus (HBV) infection with its consequent development of HBV chronic liver disease and hepatocellular carcinoma is a global mandatory goal. Fortunately, safe and effective HBV vaccines are currently available. Universal hepatitis B surface antigen HBV vaccination coverage is almost done. Growing knowledge based upon monitoring and surveillance of HBV vaccination programs has accumulated and the policy of booster vaccination has been evaluated. This review article provides an overview of the natural history of HBV infection, immune responses and the future of HBV infection. It also summarizes the updated sources, types and uses of HBV vaccines, whether in the preclinical phase or in the post-field vaccination. PMID:26140085

  9. Hepatitis C virus: A global view

    PubMed Central

    Mohamed, Amal Ahmed; Elbedewy, Tamer A; El-Serafy, Magdy; El-Toukhy, Naglaa; Ahmed, Wesam; Ali El Din, Zaniab

    2015-01-01

    Hepatitis C virus (HCV) is a global challenge; 130-175 million are chronically infected. Over 350000 die each year from HCV. Chronic HCV is the primary cause of cirrhosis, hepatocellular carcinoma (HCC), and end-stage liver disease. Management of chronic HCV is aimed at preventing cirrhosis, reducing the risk of HCC, and treating extra hepatic complications. New treatments for chronic HCV has been devoted based on direct-acting antivirals, as pegylated interferon (peginterferon) is responsible for many side effects and limits treatment access. Sofosbuvir is the first compound to enter the market with Peginterferon-free combination regimens. PMID:26609344

  10. Hepatitis C virus: A global view.

    PubMed

    Mohamed, Amal Ahmed; Elbedewy, Tamer A; El-Serafy, Magdy; El-Toukhy, Naglaa; Ahmed, Wesam; Ali El Din, Zaniab

    2015-11-18

    Hepatitis C virus (HCV) is a global challenge; 130-175 million are chronically infected. Over 350000 die each year from HCV. Chronic HCV is the primary cause of cirrhosis, hepatocellular carcinoma (HCC), and end-stage liver disease. Management of chronic HCV is aimed at preventing cirrhosis, reducing the risk of HCC, and treating extra hepatic complications. New treatments for chronic HCV has been devoted based on direct-acting antivirals, as pegylated interferon (peginterferon) is responsible for many side effects and limits treatment access. Sofosbuvir is the first compound to enter the market with Peginterferon-free combination regimens. PMID:26609344

  11. Induced immunity against hepatitis B virus

    PubMed Central

    Said, Zeinab Nabil Ahmed; Abdelwahab, Kouka Saadeldin

    2015-01-01

    Prevention of hepatitis B virus (HBV) infection with its consequent development of HBV chronic liver disease and hepatocellular carcinoma is a global mandatory goal. Fortunately, safe and effective HBV vaccines are currently available. Universal hepatitis B surface antigen HBV vaccination coverage is almost done. Growing knowledge based upon monitoring and surveillance of HBV vaccination programs has accumulated and the policy of booster vaccination has been evaluated. This review article provides an overview of the natural history of HBV infection, immune responses and the future of HBV infection. It also summarizes the updated sources, types and uses of HBV vaccines, whether in the preclinical phase or in the post-field vaccination. PMID:26140085

  12. The hepatitis delta virus: Replication and pathogenesis.

    PubMed

    Sureau, Camille; Negro, Francesco

    2016-04-01

    Hepatitis delta virus (HDV) is a defective virus and a satellite of the hepatitis B virus (HBV). Its RNA genome is unique among animal viruses, but it shares common features with some plant viroids, including a replication mechanism that uses a host RNA polymerase. In infected cells, HDV genome replication and formation of a nucleocapsid-like ribonucleoprotein (RNP) are independent of HBV. But the RNP cannot exit, and therefore propagate, in the absence of HBV, as the latter supplies the propagation mechanism, from coating the HDV RNP with the HBV envelope proteins for cell egress to delivery of the HDV virions to the human hepatocyte target. HDV is therefore an obligate satellite of HBV; it infects humans either concomitantly with HBV or after HBV infection. HDV affects an estimated 15 to 20 million individuals worldwide, and the clinical significance of HDV infection is more severe forms of viral hepatitis--acute or chronic--, and a higher risk of developing cirrhosis and hepatocellular carcinoma in comparison to HBV monoinfection. This review covers molecular aspects of HDV replication cycle, including its interaction with the helper HBV and the pathogenesis of infection in humans. PMID:27084031

  13. Effect of roxarsone inclusion in the diet on the performance and hepatic lipid metabolism of laying Tsaiya duck.

    PubMed

    Chen, K L; Wu, C P; Chiou, P W

    2000-07-01

    1. The aim of this study was to examine the effects of roxarsone (3-nitro-4-hydroxyphenylarsonic acid) inclusion in the diet on the performance, liver function and lipid metabolism in the liver of laying Brown Tsaiya ducks. 2. Sixty 36-week-old laying ducks were selected and allocated at random into 4 dietary treatments with 3 replications for each treatment. Feeding was for 7 weeks with 3 weeks of experimental diets followed by a 4 week withdrawal period. The experimental diets were supplemented with 0, 50, 100 and 300 mg/kg roxarsone, respectively 3. Dietary inclusion of 50 or 100 mg/kg roxarsone did not significantly promote performance. Inclusion of 300 mg/kg significantly depressed (P<0.05) performance, liver weight and content, serum triacylglycerol (TG), serum nonesterified fatty acid (NEFA) and increased (P<0.05) cholesterol, creatine kinase (CK) and aspartate aminotransferase (AST) in the serum at the end of 3 weeks on the experimental diet. 4. Laying characteristics returned to normal 4 weeks after withdrawal of roxarsone. The liver weight, fat and TG in the liver and serum concentrations of TG, NEFA, high density lipoprotein (HDL) and AST increased significantly (P<0.05), while the level of very low density lipoprotein (VLDL) decreased (P<0.05) at the end of the withdrawal period. More prominent vacuolised hepatic fatty cells were observed in laying ducks treated with 300 mg/kg of roxarsone. PMID:11081432

  14. Differences in innate immune responses to H5N1 highly pathogenic avian influenza virus infection between Pekin, Muscovy and Mallard ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ducks have been implicated in the dissemination and evolution of H5N1 highly pathogenic avian influenza (HPAI) viruses. However, differences in pathogenicity and response to vaccination have been observed between different duck species. In this study we examined the pathogenicity of H5N1 HPAI viru...

  15. Natural reservoirs for homologs of hepatitis C virus.

    PubMed

    Pfaender, Stephanie; Brown, Richard Jp; Pietschmann, Thomas; Steinmann, Eike

    2014-03-01

    Hepatitis C virus is considered a major public health problem, infecting 2%-3% of the human population. Hepatitis C virus infection causes acute and chronic liver disease, including chronic hepatitis, cirrhosis and hepatocellular carcinoma. In fact, hepatitis C virus infection is the most frequent indication for liver transplantation and a vaccine is not available. Hepatitis C virus displays a narrow host species tropism, naturally infecting only humans, although chimpanzees are also susceptible to experimental infection. To date, there is no evidence for an animal reservoir of viruses closely related to hepatitis C virus which may have crossed the species barrier to cause disease in humans and resulted in the current pandemic. In fact, due to this restricted host range, a robust immunocompetent small animal model is still lacking, hampering mechanistic analysis of virus pathogenesis, immune control and prophylactic vaccine development. Recently, several studies discovered new viruses related to hepatitis C virus, belonging to the hepaci- and pegivirus genera, in small wild mammals (rodents and bats) and domesticated animals which live in close contact with humans (dogs and horses). Genetic and biological characterization of these newly discovered hepatitis C virus-like viruses infecting different mammals will contribute to our understanding of the origins of hepatitis C virus in humans and enhance our ability to study pathogenesis and immune responses using tractable animal models. In this review article, we start with an introduction on the genetic diversity of hepatitis C virus and then focus on the newly discovered viruses closely related to hepatitis C virus. Finally, we discuss possible theories about the origin of this important viral human pathogen. PMID:26038514

  16. Development of a Blocking ELISA for Detection of Serum Neutralizing Antibodies against Newly Emerged Duck Tembusu Virus

    PubMed Central

    Li, Xuesong; Li, Guoxin; Teng, Qiaoyang; Yu, Lei; Wu, Xiaogang; Li, Zejun

    2012-01-01

    Background Since April 2010, domesticated ducks in China have been suffering from an emerging infectious disease characterized by retarded growth, high fever, loss of appetite, decline in egg production, and death. The causative agent was identified as a duck Tembusu virus (DTMUV), a member of the Ntaya virus (NTAV) group within the genus Flavivirus, family Flaviviridae. DTMUV is highly contagious and spreads rapidly in many species of ducks. More than 10 million shelducks have been infected and approximately 1 million died in 2010. The disease remains a constant threat to the duck industry; however, it is not known whether DTMUV can infect humans or other mammalians, despite the fact that the virus has spread widely in southeast China, one of the most densely populated areas in the world. The lack of reliable methods to detect the serum antibodies against DTMUV has limited our ability to conduct epidemiological investigations in various natural hosts and to evaluate the efficiency of vaccines to DTMUV. Methodology/Principal Findings A neutralizing monoclonal antibody (mAb) 1F5 binding specifically to the E protein was developed. Based on the mAb, a blocking enzyme-linked immunosorbent assay (ELISA) was developed for the detection of neutralizing antibodies against DTMUV. The average value of percent inhibition (PI) of 350 duck serum samples obtained from DTMUV-free farms was 1.0% ±5.8% (mean ± SD). The selected cut-off PI values for negative and positive sera were 12.6% (mean +2SD) and 18.4% (mean +3SD), respectively. When compared with a serum neutralizing antibody test (SNT) using chicken embryonated eggs, the rate of coincidence was 70.6% between the blocking ELISA and SNT, based on the titration of 20 duck DTMUV-positive serum samples. Conclusions/Significance The blocking ELISA based on a neutralizing mAb allowed rapid, sensitive, and specific detection of neutralization-related antibodies against DTMUV. PMID:23300851

  17. Diagnostic challenges of hepatitis C virus infections.

    PubMed

    Huber, K; Sebesta, C; Worofka, B; Kittl, E; Hofmann, J; Klar, S; Hinterberger, W; Bauer, K

    1998-01-01

    In less than 10 years, tremendous progress has been made in our understanding of the biology of hepatitis C virus. Since it was defined as the causal agent of most hepatitis non-A, non-B infections in 1989, clinical laboratories now have access to powerful new techniques for the diagnosis of infection and control of therapy. Identification of the specific virus strain in the patients as well as measurement of the individual viral load and the prediction of a possible therapeutic success have become routine procedures. This effort is warranted because the treatment options are still limited, with alpha-interferon being the only approved drug. No new treatment regimens have emerged yet from the wealth of data from subtyping and quantitating. PMID:15094859

  18. Epidemiology of hepatitis E virus in Iran.

    PubMed

    Taherkhani, Reza; Farshadpour, Fatemeh

    2016-06-14

    Iran is known as an endemic country for hepatitis E virus (HEV) infection, while there are variations in the epidemiology of HEV infection throughout the country. The available epidemiological studies in different regions of Iran show HEV seroprevalence of 1.1%-14.2% among general population, 4.5% -14.3% among blood donors, 6.1%-22.8% among injecting drug users, 6.3%-28.3% among hemodialysis patients, 1.6%-11.3% among patients infected with other hepatitis viruses, 27.5% among patients with chronic liver disease, 30.8% among kidney transplant recipient patients, and 10%-16.4% among human immunodeficiency virus-infected patients. These variations reflect differences in the status of public health and hygiene, risk factors, and routes of transmission in different regions and groups. Therefore, it is necessary to review the epidemiology of HEV infection to determine the most prevalent risk factors and routes of transmission, and to evaluate the effectiveness of preventive strategies employed in the public health services of the country. Moreover, the other epidemiological aspects of HEV, including the genotypic pattern, extra hepatic manifestations, and incidence of chronic infection need to be investigated among Iranian population to expand the current knowledge on the epidemiology of HEV and to clarify the real burden of HEV infection. Therefore, this review was performed to provide a general overview regarding the epidemiology of HEV in Iran. PMID:27298557

  19. Assembly of hepatitis delta virus particles.

    PubMed Central

    Ryu, W S; Bayer, M; Taylor, J

    1992-01-01

    Hepatitis delta virus (HDV) is a subviral satellite of hepatitis B virus (HBV). Since the RNA genome of HDV can replicate in cultured cells in the absence of HBV, it has been suggested that the only helper function of HBV is to supply HBV coat proteins in the assembly process of HDV particles. To examine the factors involved in such virion assembly, we transiently cotransfected cells with various hepadnavirus constructs and cDNAs of HDV and analyzed the particles released into the medium. We report that the HDV genomic RNA and the delta antigen can be packaged by coat proteins of either HBV or the related hepadnavirus woodchuck hepatitis virus (WHV). Among the three co-carboxy-terminal coat proteins of WHV, the smallest form was sufficient to package the HDV genome; even in the absence of HDV RNA, the delta antigen could be packaged by this WHV coat protein. Also, of the two co-amino-terminal forms of the delta antigen, only the larger form was essential for packaging. Images PMID:1548764

  20. Epidemiology of hepatitis E virus in Iran

    PubMed Central

    Taherkhani, Reza; Farshadpour, Fatemeh

    2016-01-01

    Iran is known as an endemic country for hepatitis E virus (HEV) infection, while there are variations in the epidemiology of HEV infection throughout the country. The available epidemiological studies in different regions of Iran show HEV seroprevalence of 1.1%-14.2% among general population, 4.5% -14.3% among blood donors, 6.1%-22.8% among injecting drug users, 6.3%-28.3% among hemodialysis patients, 1.6%-11.3% among patients infected with other hepatitis viruses, 27.5% among patients with chronic liver disease, 30.8% among kidney transplant recipient patients, and 10%-16.4% among human immunodeficiency virus-infected patients. These variations reflect differences in the status of public health and hygiene, risk factors, and routes of transmission in different regions and groups. Therefore, it is necessary to review the epidemiology of HEV infection to determine the most prevalent risk factors and routes of transmission, and to evaluate the effectiveness of preventive strategies employed in the public health services of the country. Moreover, the other epidemiological aspects of HEV, including the genotypic pattern, extra hepatic manifestations, and incidence of chronic infection need to be investigated among Iranian population to expand the current knowledge on the epidemiology of HEV and to clarify the real burden of HEV infection. Therefore, this review was performed to provide a general overview regarding the epidemiology of HEV in Iran. PMID:27298557

  1. Egg drop syndrome virus enters duck embryonic fibroblast cells via clathrin-mediated endocytosis.

    PubMed

    Huang, Jingjing; Tan, Dan; Wang, Yang; Liu, Caihong; Xu, Jiamin; Wang, Jingyu

    2015-12-01

    Previous studies of egg drop syndrome virus (EDSV) is restricted to serological surveys, disease diagnostics, and complete viral genome analysis. Consequently, the infection characteristics and entry routes of EDSV are poorly understood. Therefore, we aimed to explore the entry pathway of EDSV into duck embryonic fibroblast (DEF) cells as well as the infection characteristics and proliferation of EDSV in primary DEF and primary chicken embryo liver (CEL) cells. Transmission electron microscopy revealed that the virus triggered DEF cell membrane invagination as early as 10 min post-infection and that integrated endocytic vesicles formed at 20 min post-infection. The virus yield in EDSV-infected DEF cells treated with chlorpromazine (CPZ), sucrose, methyl-β-cyclodextrin (MβCD), or NH4Cl was measured by quantitative real-time PCR. Compared with the mock treatment, CPZ and sucrose greatly inhibited the production of viral progeny in a dose-dependent manner, while MβCD treatment did not result in a significant difference. Furthermore, NH4Cl had a strong inhibitory effect on the production of EDSV progeny. In addition, indirect immunofluorescence demonstrated that virus particles clustered on the surface of DEF cells treated with CPZ or sucrose. These results indicate that EDSV enters DEF cells through clathrin-mediated endocytosis followed by a pH-dependent step, which is similar to the mechanism of entry of human adenovirus types 2 and 5. PMID:26200954

  2. Characterization of a novel H3N2 influenza virus isolated from domestic ducks in China.

    PubMed

    Li, Chong; Yu, Meng; Liu, Litao; Sun, Honglei

    2016-08-01

    Cases of human infection with a novel H7N9 avian influenza virus (AIV) were first reported in March 2013, which caused 115 deaths within a single year. Beyond that, other subtypes of H7 AIV were isolated from poultry in eastern China during the same period, including H7N7 and H7N2 AIV. In the present study, a subtype H3N2 AIV was isolated from ducks from Anhui Province, China. Sequence and phylogenetic analyses revealed that seven gene segments of this virus showed the highest sequence homology with that of the H7 subtype influenza virus, which is presumed to be the reassortants of the H3 and H7 subtypes AIV. The present study also reconfirmed that the reassortment between the H7 subtype and waterfowl-originating AIVs universally occurred in waterfowl. Animal inoculation tests showed that the virus has low pathogenicity in chickens; however, it could be replicated in the lungs of mice. The emergence of this H3N2 isolate emphasizes the importance of enhancing the surveillance of waterfowl-originating AIVs, the identification of novel reassortant strains, and characterization of their biological properties. PMID:27000112

  3. Molecular Basis of Replication of Duck H5N1 Influenza Viruses in a Mammalian Mouse Model

    PubMed Central

    Li, Zejun; Chen, Hualan; Jiao, Peirong; Deng, Guohua; Tian, Guobin; Li, Yanbing; Hoffmann, Erich; Webster, Robert G.; Matsuoka, Yumiko; Yu, Kangzhen

    2005-01-01

    We recently analyzed a series of H5N1 viruses isolated from healthy ducks in southern China since 1999 and found that these viruses had progressively acquired the ability to replicate and cause disease in mice. In the present study, we explored the genetic basis of this change in host range by comparing two of the viruses that are genetically similar but differ in their ability to infect mice and have different pathogenicity in mice. A/duck/Guangxi/22/2001 (DKGX/22) is nonpathogenic in mice, whereas A/duck/Guangxi/35/2001 (DKGX/35) is highly pathogenic. We used reverse genetics to create a series of single-gene recombinants that contained one gene from DKGX/22 and the remaining seven gene segments from DKGX/35. We find that the PA, NA, and NS genes of DKGX/22 could attenuate DKGX/35 virus to some extent, but PB2 of DKGX/22 virus attenuated the DKGX/35 virus dramatically, and an Asn-to-Asp substitution at position 701 of PB2 plays a key role in this function. Conversely, of the recombinant viruses in the DKGX/22 background, only the one that contains the PB2 gene of DKGX/35 was able to replicate in mice. A single amino acid substitution (Asp to Asn) at position 701 of PB2 enabled DKGX/22 to infect and become lethal for mice. These results demonstrate that amino acid Asn 701 of PB2 is one of the important determinants for this avian influenza virus to cross the host species barrier and infect mice, though the replication and lethality of H5N1 influenza viruses involve multiple genes and may result from a constellation of genes. Our findings may help to explain the expansion of the host range and lethality of the H5N1 influenza viruses to humans. PMID:16140781

  4. Recombinant infectious bursal disease virus carrying hepatitis C virus epitopes.

    PubMed

    Upadhyay, Chitra; Ammayappan, Arun; Patel, Deendayal; Kovesdi, Imre; Vakharia, Vikram N

    2011-02-01

    The delivery of foreign epitopes by a replicating nonpathogenic avian infectious bursal disease virus (IBDV) was explored. The aim of the study was to identify regions in the IBDV genome that are amenable to the introduction of a sequence encoding a foreign peptide. By using a cDNA-based reverse genetics system, insertions or substitutions of sequences encoding epitope tags (FLAG, c-Myc, or hepatitis C virus epitopes) were engineered in the open reading frames of a nonstructural protein (VP5) and the capsid protein (VP2). Attempts were also made to generate recombinant IBDV that displayed foreign epitopes in the exposed loops (P(BC) and P(HI)) of the VP2 trimer. We successfully recovered recombinant IBDVs expressing c-Myc and two different virus-neutralizing epitopes of human hepatitis C virus (HCV) envelope glycoprotein E in the VP5 region. Western blot analyses with anti-c-Myc and anti-HCV antibodies provided positive identification of both the c-Myc and HCV epitopes that were fused to the N terminus of VP5. Genetic analysis showed that the recombinants carrying the c-Myc/HCV epitopes maintained the foreign gene sequences and were stable after several passages in Vero and 293T cells. This is the first report describing efficient expression of foreign peptides from a replication-competent IBDV and demonstrates the potential of this virus as a vector. PMID:21106739

  5. Cell entry of hepatitis C virus

    SciTech Connect

    Bartosch, Birke . E-mail: Birke.Bartosch@ens-lyon.fr; Cosset, Francois-Loic . E-mail: Francois-Loic.Cosset@ens-lyon.fr

    2006-04-25

    Hepatitis C virus (HCV), an important human pathogen, is an enveloped, positive-stranded RNA virus classified in the hepacivirus genus of the Flaviviridae family. Cell attachment of flaviviruses generally leads to endocytosis of bound virions. Systems that support HCV replication and particle formation in vitro are emerging only now, 16 years after the discovery of the virus. Albeit this limitation, the route of HCV cell entry as well as 'capture' molecules involved in low-affinity interactions for the initial contact of HCV with target cells and potential high-affinity receptor candidates that may mediate HCV trafficking and fusion has been described. The objective of this review is to summarize the contribution of different HCV model systems to our current knowledge about structure of the HCV GPs E1 and E2 and their roles in cell entry comprising cell attachment, interactions with cellular receptors, endocytosis, and fusion.

  6. Thermostability of subpopulations of H2N3 influenza virus isolates from mallard ducks.

    PubMed

    Negovetich, Nicholas J; Webster, Robert G

    2010-09-01

    Maintenance of avian influenza virus in waterfowl populations requires that virions remain infectious while in the environment. Temperature has been shown to negatively correlate with persistence time, which is the duration for which virions are infectious. However, thermostability can vary between isolates regardless of subtype, and it is not known whether this variation occurs when host and geographic location of isolation are controlled. In this study, we analyzed the thermostabilities of 7 H2N3 viruses isolated from mallard ducks in Alberta, Canada. Virus samples were incubated at 37 degrees C and 55 degrees C, and infectivity titers were calculated at different time points. Based on the rate of infectivity inactivation at 37 degrees C, isolates could be grouped into either a thermosensitive or thermostable fraction for both egg- and MDCK-grown virus populations. Titers decreased more rapidly for isolates incubated at 55 degrees C, and this loss of infectivity occurred in a nonlinear, 2-step process, which is in contrast with the consensus on thermostability. This suggests that stock samples contain a mixture of subpopulations with different thermostabilities. The rate of decrease for the sensitive fraction was approximately 14 times higher than that for the stable fraction. The presence of subpopulations is further supported by selection experiments and plaque purification, both of which result in homogenous populations that exhibit linear decreases of infectivity titer. Therefore, variation of thermostability of influenza virus isolates begins at the level of the population. The presence of subpopulations with high thermostability suggests that avian viruses can persist in water longer than previously estimated, thus increasing the probability of transmission to susceptible hosts. PMID:20610728

  7. Isolation and identification of Duck tembusu virus strain lH and development of latex-agglutination diagnostic method for rapid detection of antibodies.

    PubMed

    Wang, Quanxi; Wen, Yaping; Yifan Huang; Wu, Yijian; Cai, Yilong; Xu, Lihui; Wang, Changkang; Li, Ang; Wu, Baocheng; Chen, Jilong

    2014-12-01

    SUMMARY. An outbreak of egg-drop syndrome occurred on a Sheldrake duck farm in Longhai in Fujian Province, China, in 2012. The main clinical symptoms were sharply reduced egg production, crooked necks, and death. We isolated the virus from the sick ducks, identified it, and observed the histopathologic changes after viral infection. We detected viral RNA in the blood and feces of the infected ducks and developed a latex-agglutination diagnostic method to detect anti-Tembusu-virus antibodies. Our results show that the pathogenic virus is a Tembusu virus. The histopathologic changes included follicular cell degeneration and necrosis, follicular cavity filled with blood cells, massive necrosis in the brain, and degeneration and necrosis of the nerve and glial cells. When the transmission of the virus in the infected ducks was studied, the duck blood was positive for viral nucleic acid for up to 29 days, and the feces were positive for viral nucleic acid for up to 13 days. We successfully established a simple, rapid, and easy- to-use latex-agglutination diagnostic method for the detection of antibodies against duck Tembusu virus. PMID:25619007

  8. First survey of the occurrence of duck enteritis virus (DEV) in free-ranging Polish water birds.

    PubMed

    Woźniakowski, Grzegorz; Samorek-Salamonowicz, Elzbieta

    2014-06-01

    Duck plague (DP) caused by anatid herpesvirus 1, also called duck enteritis virus (DEV), presents one of the most important concerns in mass waterfowl production. Apart from geese and ducks, free-ranging water birds are the most notorious infection carriers. The epidemiology of DEV in Western Europe remains unknown. Therefore, it was reasonable to conduct a study on its occurrence using modern but simple real-time loop-mediated isothermal amplification (LAMP). Analysis of 132 field isolates showed the presence of DEV in 96 birds (72.7 %), and it was found predominantly in wild ducks (Anas platyrhynchos) and mute swans (Cygnus olor). This virus was also found in graylag geese (Anser anser), tundra bean geese (Anser fabalis), and grey herons (Ardea cinerea). The results were recorded as green colour of positive samples, fluorescence under ultraviolet light, and florescent curves in a real-time PCR system. This study indicates the high prevalence of DEV among free-ranging water birds in Poland and the possible transmission to other birds settling in the water environment. This is the first report of DEV detection among free-ranging water birds in Poland. PMID:24327092

  9. [Hepatitis E virus: Blood transfusion implications].

    PubMed

    Gallian, P; Piquet, Y; Assal, A; Djoudi, R; Chiaroni, J; Izopet, J; Tiberghien, P

    2014-11-01

    Hepatitis E virus (HEV) is a non-enveloped RNA virus transmitted by the fecal-oral route. Autochthonous hepatitis E occurring in developed countries is caused by genotypes 3 and 4 and is a zoonotic infection. Humans are infected mostly after ingestion of undercooked meat from infected animals. Most HEV 3 and 4 infections are clinically inapparent. However, genotype 3 (HEV 3) can lead to chronic hepatitis in immuno-compromised patients such as organ-transplant recipients and patients with haematological malignancies. In Europe, HEV 3 is implicated in transfusion-transmitted HEV infection. In France, as observed in several European countries, prevalence of HEV RNA and specific IgG antibodies are high indicating that viral circulation is important. The systematic HEV NAT screening of blood donations used for preparation of solvent detergent plasma indicate that 1 to 2218 donation is infected by HEV RNA. The need or implementation's impacts of safety measures to prevent HEV transmission by blood transfusion are under reflexion by French's health authorities. The HEV NAT screening is the only available tool of prevention. Alternative strategies are under investigation including individual or mini pool NAT testing all or part of blood donations. PMID:25267201

  10. Hepatitis

    MedlinePlus

    ... has been associated with drinking contaminated water. Hepatitis Viruses Type Transmission Prognosis A Fecal-oral (stool to ... risk for severe disease. Others A variety of viruses can affect the liver Signs and Symptoms Hepatitis ...

  11. Antiviral effect of resveratrol in ducklings infected with virulent duck enteritis virus.

    PubMed

    Zhao, Xinghong; Xu, Jiao; Song, Xu; Jia, Ruilin; Yin, Zhongqiong; Cheng, Anchun; Jia, Renyong; Zou, Yuanfeng; Li, Lixia; Yin, Lizi; Yue, Guizhou; Lv, Cheng; Jing, Bo

    2016-06-01

    Duck enteritis virus (DEV) is a double-stranded DNA virus belonging to the alphaherpesvirinae subfamily of the herpesviridae. Although vaccines were wildly used in controlling this disease, some infection could still not be prevented and led to significant economic losses as a result of mortality and decreased egg production. However, there is no antiviral drug against DEV. Resveratrol was identified to exert its antiviral activity by inhibiting the DEV replication in preliminary investigations. In the present study, we confirmed that resveratrol significantly reduced the mortality of ducklings which infected with a virulent strain of DEV. With resveratrol treatment, the survival rate increased by almost 80% at 8 days post infection (dpi). Pathological symptoms of ducklings caused by DEV were also relieved by resveratrol. The virus load in blood and tissues were effectively depressed when compared with the untreated group. In the assay of immune cytokines, the resveratrol exerted a dual-regulation effect. These results suggest that resveratrol is expected to be a new alternative control measure for DEV infection. PMID:27040314

  12. Hepatitis B virus infection in immigrant populations

    PubMed Central

    Coppola, Nicola; Alessio, Loredana; Pisaturo, Mariantonietta; Macera, Margherita; Sagnelli, Caterina; Zampino, Rosa; Sagnelli, Evangelista

    2015-01-01

    Hepatitis B virus (HBV) is the most common cause of hepatitis worldwide, with nearly 350 million people chronically infected and 600000 deaths per year due to acute liver failure occurring during acute hepatitis or, more frequently, in HBV-related liver cirrhosis or hepatocellular carcinoma. Ongoing immigration from countries with a high HBV endemicity to those with a low HBV endemicity warrants particular attention to prevent the spread of HBV infection to the native population. This review article analyzes the epidemiology and virological and clinical characteristics of HBV infection in immigrant populations and in their host countries, and suggests prophylactic measures to prevent the spread of this infection. Among the immigrants from different geographical areas, those from South East Asia and sub-Saharan Africa show the highest prevalences of hepatitis B surface antigen (HBsAg) carriers, in accordance with the high endemicity of the countries of origin. The molecular characteristics of HBV infection in immigrants reflect those of the geographical areas of origin: HBV genotype A and D predominate in immigrants from Eastern Europe, B and C in those from Asia and genotype E in those from Africa. The literature data on the clinical course and treatment of HBsAg-positive immigrants are scanty. The management of HBV infection in immigrant populations is difficult and requires expert personnel and dedicated structures for their assistance. The social services, voluntary operators and cultural mediators are essential to achieve optimized psychological and clinical intervention. PMID:26730274

  13. Type III interferon gene expression in response to influenza virus infection in chicken and duck embryonic fibroblasts.

    PubMed

    Zhang, Zhijie; Zou, Tingting; Hu, Xiaotong; Jin, Hong

    2015-12-01

    Type III interferons (IFN-λs) comprise a group of newly identified antiviral cytokines that are functionally similar to type I IFNs and elicit first-line antiviral responses. Recently, type III IFNs were identified in several species; however, little information is available about type III IFNs in ducks. We compared the expression of type III IFNs and their receptor in chicken embryonic fibroblasts (CEFs) and duck embryonic fibroblasts (DEFs) in response to influenza virus infection. The results showed that the expression of type III IFNs was upregulated in both DEFs and CEFs following infection with H1N1 influenza virus or treatment with poly (I:C), and expression levels were significantly higher in CEFs than in DEFs at each time point. The expression of the receptor for type III IFNs (IL-28Rα) was also upregulated following infection with H1N1 virus or treatment with poly (I:C) and was significantly higher in CEFs than in DEFs at each time point. The expression of the receptor for type III IFNs occurred from 8 hpi and remained at similar levels until 36 hpi in CEFs, but the expression level was elevated from 36 hpi in DEFs. These findings revealed the existence of distinct expression patterns for type III IFNs in chickens and ducks in response to influenza virus infection. The provided data are fundamentally useful in furthering our understanding of type III IFNs and innate antiviral responses in different species. PMID:26598110

  14. Ribonucleoprotein complexes of hepatitis delta virus.

    PubMed Central

    Ryu, W S; Netter, H J; Bayer, M; Taylor, J

    1993-01-01

    Human hepatitis delta virus (HDV) is a subviral satellite agent of hepatitis B virus (HBV). The envelope proteins of HDV are provided by the helper virus, HBV, but very little is known about the internal structure of HDV. The particles contain multiple copies of the delta antigen and an unusual RNA genome that is small, about 1,700 nucleotides in length, single stranded, and circular. By using UV cross-linking, equilibrium density centrifugation, and immunoprecipitation, we obtained evidence consistent with the interpretation that delta antigen and genomic RNA form a stable ribonucleoprotein (RNP) complex within the virion. Furthermore, electron-microscopic examination of the purified viral RNP revealed a roughly spherical core-like structure with a diameter of 18.7 +/- 2.5 nm. We also isolated HDV-specific RNP structures from the nuclei of cells undergoing HDV genome replication; both the genome and antigenome (a complement of the genome) of HDV were found to be in such complexes. From the equilibrium density analyses of the viral and nuclear RNPs, we were able to deduce the number of molecules of delta antigen per molecule of HDV RNA. For virions, this number was predominantly ca. 70, which was larger than for the nuclear RNPs, which were more heterogeneous, with an average value of ca. 30. Images PMID:8497052

  15. Different routes of inoculation impact infectivity and pathogenesis of H5N1 high pathogenicity avian influenza virus infection in chickens and domestic ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The H5N1 type A influenza viruses classified as Qinghai-like virus (clade 2.2) are a unique lineage of type A influenza viruses with the capacity to produce significant disease and mortality in gallinaceous birds and water fowl including ducks. The objective of this study was to determine the suscep...

  16. EFFECT OF CHLORINE TREATMENT ON INFECTIVITY OF HEPATITIS A VIRUS

    EPA Science Inventory

    This study examined the effect of chlorine treatment on the infectivity of hepatitis A virus (HAV). Prodromal chimpanzee feces, shown to induce hepatitis in marmosets (Saguinus sp.), was clarified, and the virus was precipitated with 7% polyethylene glycol 6000, harvested and res...

  17. Characterization of a prototype strain of hepatitis E virus.

    PubMed Central

    Tsarev, S A; Emerson, S U; Reyes, G R; Tsareva, T S; Legters, L J; Malik, I A; Iqbal, M; Purcell, R H

    1992-01-01

    A strain of hepatitis E virus (SAR-55) implicated in an epidemic of enterically transmitted non-A, non-B hepatitis, now called hepatitis E, was characterized extensively. Six cynomolgus monkeys (Macaca fascicularis) were infected with a strain of hepatitis E virus from Pakistan. Reverse transcription-polymerase chain reaction was used to determine the pattern of virus shedding in feces, bile, and serum relative to hepatitis and induction of specific antibodies. Virtually the entire genome of SAR-55 (7195 nucleotides) was sequenced. Comparison of the sequence of SAR-55 with that of a Burmese strain revealed a high level of homology except for one region encoding 100 amino acids of a putative nonstructural polyprotein. Identification of this region as hypervariable was obtained by partial sequencing of a third isolate of hepatitis E virus from Kirgizia. Images PMID:1731327

  18. Host restriction factors for hepatitis C virus

    PubMed Central

    Zhou, Li-Ya; Zhang, Lei-Liang

    2016-01-01

    Host-hepatitis C virus (HCV) interactions have both informed fundamental concepts of viral replication and pathogenesis and provided novel insights into host cell biology. These findings are illustrated by the recent discovery of host-encoded factors that restrict HCV infection. In this review, we briefly discuss these restriction factors in different steps of HCV infection. In each case, we discuss how these restriction factors were identified, the mechanisms by which they inhibit HCV infection and their potential contribution to viral pathogenesis. PMID:26819515

  19. Biosensors for hepatitis B virus detection.

    PubMed

    Yao, Chun-Yan; Fu, Wei-Ling

    2014-09-21

    A biosensor is an analytical device used for the detection of analytes, which combines a biological component with a physicochemical detector. Recently, an increasing number of biosensors have been used in clinical research, for example, the blood glucose biosensor. This review focuses on the current state of biosensor research with respect to efficient, specific and rapid detection of hepatitis B virus (HBV). The biosensors developed based on different techniques, including optical methods (e.g., surface plasmon resonance), acoustic wave technologies (e.g., quartz crystal microbalance), electrochemistry (amperometry, voltammetry and impedance) and novel nanotechnology, are also discussed. PMID:25253948

  20. Recent advances in Hepatitis E virus.

    PubMed

    Meng, X J

    2010-03-01

    Hepatitis E virus (HEV), the causative agent of hepatitis E, belongs to the family Hepeviridae. At least four major genotypes of HEV have been recognized: genotypes 1 and 2 are restricted to humans and associated with epidemics in developing countries, whereas genotypes 3 and 4 are zoonotic and infect humans and several other animals in both developing and industrialized countries. Besides humans, strains of HEV have been genetically identified from swine, chickens, sika deer, mongeese, and rabbits. The genome of HEV consists of three open reading frames (ORFs): ORF1 codes for nonstructural proteins, ORF2 codes for capsid protein, and ORF3 codes for a small multifunctional protein. The ORF2 and ORF3 proteins are translated from a single bicistronic mRNA and overlap each other but neither overlaps ORF1. The recent determination of the 3D crystal structure of the HEV capsid protein should facilitate the development of vaccines and antivirals. The identification and characterization of animal strains of HEV from pigs and chickens and the demonstrated ability of cross-species infection by swine HEV raise public health concerns for zoonosis. Accumulating evidence indicated that hepatitis E is a zoonotic disease and pigs and more likely other animal species are reservoirs for HEV. This article provides an overview of the recent advances in hepatitis E and its causative agent, including nomenclature and genomic organization, gene expression and functions, 3D structure of the virions, changing perspectives on higher mortality during pregnancy and chronic hepatitis E, animal reservoirs, zoonotic risk, food safety, and novel animal models. PMID:20040046

  1. Comparative hepatic cytochrome P450 activities and contaminant concentrations in caged carp and juvenile ducks

    SciTech Connect

    O`Keefe, P.; Gierthy, J.; Connor, S.; Bush, B.; Hong, C.S.; Wood, L.; Clayton, W.; Storm, R.

    1995-12-31

    Juvenile carp (Cyprinius carpio) weighing approx. 60 g were placed in cages located on the surface of sediments near an aluminum plant and an automobile parts plant in the Massena area of the St. Lawrence River. Fish were removed at weekly intervals over a 35 day exposure period and composited samples of liver tissue, cranial lipid, and fillet tissue were prepared for analysis of polynuclear aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs/PCDFs). Liver tissue was also stored at {minus}80 C for determination of microsomal Cytochrome P450 activity using the aryl hydrocarbon hydroxylase (AHH) assay. A control exposure was carried out upstream at an uncontaminated site. Juvenile pre-flight ducks (mallards, gadwalls, wood ducks and common mergansers) were collected in the contaminated areas on the St. Lawrence and on the Hudson River two to three months after hatching. Control pre-flight mallards, wood ducks and common mergansers were collected from remote lakes in the Addirondack State Park. Samples of subcutaneous fat and liver tissue were removed for analysis as described above for the carp. There was a three fold increase in AHH activity in the carp liver tissue at the end of the 35 day exposure period and there was a similar increase it activity for the mallards, common mergansers and wood ducks compared to controls. For each species the enzyme activity increases will be compared to the contaminant concentrations.

  2. Molecular Biology of Hepatitis B Virus Infection

    PubMed Central

    Seeger, Christoph; Mason, William S.

    2015-01-01

    Human hepatitis B virus (HBV) is the prototype of a family of small DNA viruses that productively infect hepatocytes, the major cell of the liver, and replicate by reverse transcription of a terminally redundant viral RNA, the pregenome. Upon infection, the circular, partially double-stranded virion DNA is converted in the nucleus to a covalently closed circular DNA (cccDNA) that assembles into a minichromosome, the template for viral mRNA synthesis. Infection of hepatocytes is non-cytopathic. Infection of the liver may be either transient (<6 months) or chronic and life long, depending on the ability of the host immune response to clear the infection. Chronic infections can cause immune mediated liver damage progressing to cirrhosis and hepatocellular carcinoma (HCC). The mechanisms of carcinogenesis are unclear. Antiviral therapies with nucleoside analog inhibitors of viral DNA synthesis delay sequelae, but cannot cure HBV infections due to the persistence of cccDNA in hepatocytes. PMID:25759099

  3. Culture systems for hepatitis E virus.

    PubMed

    Okamoto, Hiroaki

    2013-02-01

    The lack of an efficient cell culture system for hepatitis E virus (HEV) has greatly hampered detailed analyses of this virus. The first efficient cell culture systems for HEV that were developed were capable of secreting infectious HEV progenies in high titers into culture media, using PLC/PRF/5 cells derived from human hepatocellular carcinoma and A549 cells derived from human lung cancer as host cells. The success achieved with the original genotype 3 JE03-1760F strain has now been extended to various HEV strains in fecal and serum samples obtained from hepatitis E patients and to HEV strains in fecal and serum samples and liver tissues obtained from pigs and wild boar across species barriers. In addition, infectious HEV cDNA clones of the wild-type JE03-1760F strain and its variants have been engineered. Cell culture-generated HEV particles and those in circulating blood were found to be associated with lipids and open reading frame 3 (ORF3) protein, thereby likely contributing to the assembly and release of HEV from infected cells both in vivo and in vitro. The ORF3 protein interacts with the tumor susceptibility gene 101, a critical cellular protein required for the budding of enveloped viruses, through the Pro, Ser, Ala, and Pro (PSAP) motif in infected cells; ORF3 is co-localized with multivesicular bodies (MVBs) in the cytoplasm of infected cells, thus suggesting that HEV requires the MVB pathway for the egress of virus particles. This article reviews the development of efficient cell culture systems for a wide variety of infectious HEV strains obtained from humans, pigs, and wild boar, and also provides details of a new model for virion egress. PMID:23104469

  4. Anti-hepatitis B virus activities of triterpenoid saponin compound from Potentilla anserine L.

    PubMed

    Zhao, Y-L; Cai, G-M; Hong, X; Shan, L-M; Xiao, X-H

    2008-04-01

    The Tibetan herb Potentilla anserina L. has been widely used in China for many thousands of years to treat hepatitis-B. Bioassay-guided fractionation of the ethanol extract of the rhizomes led to the isolation of a triterpenoid saponin (TS) that was determined to be 2alpha,3beta,19alpha-trihydroxyurs-12-en-28-oic acid beta-D-glucopyranosyl ester. Using models of HBV infection, this compound was evaluated for its effect on HBV antigene expression in the 2.2.15 cell line in vitro and anti-hepatitis B virus (HBV) activities in Peking ducklings in vivo. Results showed that it could decrease the expression levels of HBsAg, HBeAg and HBVDNA in the 2.2.15 cell culture and the inhibitory effect was not due to the cytotoxity of the triterpenoid saponin. The antiviral study in vivo on Peking ducklings also demonstrated that this compound inhibits duck hepatitis B virus (DHBV) DNA replication. PMID:18337074

  5. Susceptibility of North American Ducks and Gulls to H5N1 Highly Pathogenic Avian Influenza Viruses

    PubMed Central

    Stallknecht, David E.; Beck, Joan R.; Suarez, David L.; Swayne, David E.

    2006-01-01

    Since 2002, H5N1 highly pathogenic avian influenza (HPAI) viruses have been associated with deaths in numerous wild avian species throughout Eurasia. We assessed the clinical response and extent and duration of viral shedding in 5 species of North American ducks and laughing gulls (Larus atricilla) after intranasal challenge with 2 Asian H5N1 HPAI viruses. Birds were challenged at ≈10 to 16 weeks of age, consistent with temporal peaks in virus prevalence and fall migration. All species were infected, but only wood ducks (Aix sponsa) and laughing gulls exhibited illness or died. Viral titers were higher in oropharyngeal swabs than in cloacal swabs. Duration of viral shedding (1–10 days) increased with severity of clinical disease. Both the hemagglutination-inhibition (HI) and agar gel precipitin (AGP) tests were able to detect postinoculation antibodies in surviving wood ducks and laughing gulls; the HI test was more sensitive than the AGP in the remaining 4 species PMID:17283615

  6. Chaperones in hepatitis C virus infection

    PubMed Central

    Khachatoorian, Ronik; French, Samuel W

    2016-01-01

    The hepatitis C virus (HCV) infects approximately 3% of the world population or more than 185 million people worldwide. Each year, an estimated 350000-500000 deaths occur worldwide due to HCV-associated diseases including cirrhosis and hepatocellular carcinoma. HCV is the most common indication for liver transplantation in patients with cirrhosis worldwide. HCV is an enveloped RNA virus classified in the genus Hepacivirus in the Flaviviridae family. The HCV viral life cycle in a cell can be divided into six phases: (1) binding and internalization; (2) cytoplasmic release and uncoating; (3) viral polyprotein translation and processing; (4) RNA genome replication; (5) encapsidation (packaging) and assembly; and (6) virus morphogenesis (maturation) and secretion. Many host factors are involved in the HCV life cycle. Chaperones are an important group of host cytoprotective molecules that coordinate numerous cellular processes including protein folding, multimeric protein assembly, protein trafficking, and protein degradation. All phases of the viral life cycle require chaperone activity and the interaction of viral proteins with chaperones. This review will present our current knowledge and understanding of the role of chaperones in the HCV life cycle. Analysis of chaperones in HCV infection will provide further insights into viral/host interactions and potential therapeutic targets for both HCV and other viruses. PMID:26783419

  7. Evaluation of Newcastle disease virus immunoassays for waterfowl using a monoclonal antibody specific for the duck immunoglobulin light chain.

    PubMed

    Kothlow, Sonja; Haüslaigner, Rafaela; Kaspers, Bernd; Grund, Christian

    2008-06-01

    In the present study a monoclonal antibody (mAb 14A3) was tested for its reactivity against serum immunoglobulin Y (IgY) of several waterfowl species, and subsequently for its applicability as anti-species antibody in common immunoassays. Western blot analyses demonstrated its broad cross-reactivity with the serum IgY light chain of different duck species: Muscovy duck (Cairina moschata), Mallard (Anas platyrhynchos), white-winged wood duck (Asarcornis scutulatus), common pintail (Dafila acuta). Reactivity was also evident with IgY of two swan species--mute swan (Cygnus olor) and black-necked swan (Sthenelides melanocoryphus)--and two goose species--domestic goose (Anser anser var. domestica) and red-breasted goose (Rufibrenta ruficollis). Applying the mAb for Newcastle disease virus (avian paramyxovirus serotype 1 [APMV-1]) test systems, its functionality within indirect immunoassays was evaluated. Using APMV-1-positive sera of domestic geese and Muscovy ducks, mAb 14A3 facilitated specific staining of APMV-1-infected cells in an immunofluorescence test. In addition, it proved to be functional in an indirect enzyme-linked immunosorbent assay (ELISA) and a western blot assay. Thus, the analysed mAb represents an attractive and versatile reagent that offers the opportunity to develop serological tests for waterfowl, allowing a high sample throughput using the ELISA technique or the fine analysis of humoral immune responses using the western blot. PMID:18568660

  8. Hepatitis B virus burden in developing countries

    PubMed Central

    Zampino, Rosa; Boemio, Adriana; Sagnelli, Caterina; Alessio, Loredana; Adinolfi, Luigi Elio; Sagnelli, Evangelista; Coppola, Nicola

    2015-01-01

    Hepatitis B virus (HBV) infection has shown an intermediate or high endemicity level in low-income countries over the last five decades. In recent years, however, the incidence of acute hepatitis B and the prevalence of hepatitis B surface antigen chronic carriers have decreased in several countries because of the HBV universal vaccination programs started in the nineties. Some countries, however, are still unable to implement these programs, particularly in their hyperendemic rural areas. The diffusion of HBV infection is still wide in several low-income countries where the prevention, management and treatment of HBV infection are a heavy burden for the governments and healthcare authorities. Of note, the information on the HBV epidemiology is scanty in numerous eastern European and Latin-American countries. The studies on molecular epidemiology performed in some countries provide an important contribution for a more comprehensive knowledge of HBV epidemiology, and phylogenetic studies provide information on the impact of recent and older migratory flows. PMID:26576083

  9. Hepatitis C virus and neurological damage

    PubMed Central

    Mathew, Shilu; Faheem, Muhammed; Ibrahim, Sara M; Iqbal, Waqas; Rauff, Bisma; Fatima, Kaneez; Qadri, Ishtiaq

    2016-01-01

    Chronic hepatitis C virus (HCV) infection exhibits a wide range of extrahepatic complications, affecting various organs in the human body. Numerous HCV patients suffer neurological manifestations, ranging from cognitive impairment to peripheral neuropathy. Overexpression of the host immune response leads to the production of immune complexes, cryoglobulins, as well as autoantibodies, which is a major pathogenic mechanism responsible for nervous system dysfunction. Alternatively circulating inflammatory cytokines and chemokines and HCV replication in neurons is another factor that severely affects the nervous system. Furthermore, HCV infection causes both sensory and motor peripheral neuropathy in the mixed cryoglobulinemia as well as known as an important risk aspect for stroke. These extrahepatic manifestations are the reason behind underlying hepatic encephalopathy and chronic liver disease. The brain is an apt location for HCV replication, where the HCV virus may directly wield neurotoxicity. Other mechanisms that takes place by chronic HCV infection due the pathogenesis of neuropsychiatric disorders includes derangement of metabolic pathways of infected cells, autoimmune disorders, systemic or cerebral inflammation and alterations in neurotransmitter circuits. HCV and its pathogenic role is suggested by enhancement of psychiatric and neurological symptoms in patients attaining a sustained virologic response followed by treatment with interferon; however, further studies are required to fully assess the impact of HCV infection and its specific antiviral targets associated with neuropsychiatric disorders. PMID:27134702

  10. Oral manifestations of hepatitis C virus infection

    PubMed Central

    Carrozzo, Marco; Scally, Kara

    2014-01-01

    Extrahepatic manifestations (EHMs) of hepatitis C virus (HCV) infection can affect a variety of organ systems with significant morbidity and mortality. Some of the most frequently reported EHM of HCV infection, involve the oral region predominantly or exclusively. Oral lichen planus (OLP) is a chronic inflammatory condition that is potentially malignant and represents cell-mediated reaction to a variety of extrinsic antigens, altered self-antigens, or super antigens. Robust epidemiological evidence support the link between OLP and HCV. As the virus may replicate in the oral mucosa and attract HCV-specific T lymphocytes, HCV may be implicated in OLP pathogenesis. Sjögren syndrome (SjS) is an autoimmune exocrinopathy, characterized by dryness of the mouth and eyes and a multitude of other systemic signs and symptoms. SjS patients have also an increased risk of non-Hodgkin lymphoma. Patients with chronic hepatitis C do frequently have histological signs of Sjögren-like sialadenitis with mild or even absent clinical symptoms. However, it is still unclear if HCV may cause a disease mimicking SjS or it is directly responsible for the development of SjS in a specific subset of patients. Oral squamous cell carcinoma is the most common oral malignant tumour and at least in some part of the world could be linked to HCV. PMID:24976694

  11. The Hepatitis E virus intraviral interactome

    PubMed Central

    Osterman, Andreas; Stellberger, Thorsten; Gebhardt, Anna; Kurz, Marisa; Friedel, Caroline C.; Uetz, Peter; Nitschko, Hans; Baiker, Armin; Vizoso-Pinto, Maria G.

    2015-01-01

    Hepatitis E virus (HEV) is an emerging virus causing epidemic acute hepatitis in developing countries as well as sporadic cases in industrialized countries. The life cycle of HEV is still poorly understood and the lack of efficient cell culture systems and animal models are the principal limitations for a detailed study of the viral replication cycle. Here we exhaustively examine all possible intraviral protein-protein interactions (PPIs) of HEV by systematic Yeast two-hybrid (Y2H) and LuMPIS screens, providing a basis for studying the function of these proteins in the viral replication cycle. Key PPIs correlate with the already published HEV 3D structure. Furthermore, we report 20 novel PPIs including the homodimerization of the RNA dependent RNA polymerase (RdRp), the self-interaction of the papain like protease, and ORF3 interactions with the papain-like protease and putative replicase components: RdRp, methylase and helicase. Furthermore, we determined the dissociation constant (Kd) of ORF3 interactions with the viral helicase, papain-like protease and methylase, which suggest a regulatory function for ORF3 in orchestrating the formation of the replicase complex. These interactions may represent new targets for antiviral drugs. PMID:26463011

  12. Hepatitis C virus and neurological damage.

    PubMed

    Mathew, Shilu; Faheem, Muhammed; Ibrahim, Sara M; Iqbal, Waqas; Rauff, Bisma; Fatima, Kaneez; Qadri, Ishtiaq

    2016-04-28

    Chronic hepatitis C virus (HCV) infection exhibits a wide range of extrahepatic complications, affecting various organs in the human body. Numerous HCV patients suffer neurological manifestations, ranging from cognitive impairment to peripheral neuropathy. Overexpression of the host immune response leads to the production of immune complexes, cryoglobulins, as well as autoantibodies, which is a major pathogenic mechanism responsible for nervous system dysfunction. Alternatively circulating inflammatory cytokines and chemokines and HCV replication in neurons is another factor that severely affects the nervous system. Furthermore, HCV infection causes both sensory and motor peripheral neuropathy in the mixed cryoglobulinemia as well as known as an important risk aspect for stroke. These extrahepatic manifestations are the reason behind underlying hepatic encephalopathy and chronic liver disease. The brain is an apt location for HCV replication, where the HCV virus may directly wield neurotoxicity. Other mechanisms that takes place by chronic HCV infection due the pathogenesis of neuropsychiatric disorders includes derangement of metabolic pathways of infected cells, autoimmune disorders, systemic or cerebral inflammation and alterations in neurotransmitter circuits. HCV and its pathogenic role is suggested by enhancement of psychiatric and neurological symptoms in patients attaining a sustained virologic response followed by treatment with interferon; however, further studies are required to fully assess the impact of HCV infection and its specific antiviral targets associated with neuropsychiatric disorders. PMID:27134702

  13. Prevalence of Hepatitis Virus Infections in an Institution for Persons with Developmental Disabilities.

    ERIC Educational Resources Information Center

    Woodruff, Bradley A.; Vazquez, Elizabeth

    2002-01-01

    A study involving 1,235 residents of Sonoma Developmental Center found 3 residents had hepatitis C virus infections, and 633 had past or current hepatitis B virus infections. The prevalence of hepatitis B virus infection rose rapidly with longer residence in institutions. Hepatitis A virus infection had occurred in 494 residents. (Contains…

  14. Protective Efficacy of a Single Dose of Baculovirus Hemagglutinin-Based Vaccine in Chickens and Ducks Against Homologous and Heterologous H5N1 Virus Infections

    PubMed Central

    Park, Eun Hye; Song, Byung Min; Yum, Jung; Kim, Ji An; Oh, Seung Kyoo; Kim, Hyun Soo; Cho, Gil Jae

    2014-01-01

    Abstract Outbreaks of the highly pathogenic H5N1 virus in poultry and humans are ongoing. Vaccination is an efficient method for prevention of H5N1 infection. Using chickens and ducks, we assessed the efficacy of a vaccine comprising H5N1 hemagglutinin (HA) protein produced in a baculovirus expression system. The immunized chickens and ducks were protected against lethal infection by H5N1 in an antigen dose-dependent manner. Complete protection against homologous challenge and partial protection against heterologous challenge were achieved in chickens immunized with 5 μg HA protein and in ducks immunized with 10 μg HA protein. The IgG antibody subtype was mainly detected in the sera and tissues, including the lungs. The neuraminidase (NA) inhibition assay was negative in immunized chickens and ducks. Our results indicated that the expressed HA protein by baculovirus was immunogenic to both chickens and ducks, and the immunized chickens and ducks were protected from the lethal infections of highly pathogenic H5N1 influenza virus, though ducks required more HA protein than chickens to be protected. Also, baculovirus HA-vaccinated poultry can be differentiated from infected poultry by NA inhibition assay. PMID:25211640

  15. Hepatitis C Virus, Insulin Resistance, and Steatosis

    PubMed Central

    Kralj, Dominik; Jukić, Lucija Virović; Stojsavljević, Sanja; Duvnjak, Marko; Smolić, Martina; Čurčić, Ines Bilić

    2016-01-01

    Hepatitis C virus (HCV) is one of the main causes of liver disease worldwide. Liver steatosis is a common finding in many hepatic and extrahepatic disorders, the most common being metabolic syndrome (MS). Over time, it has been shown that the frequent coexistence of these two conditions is not coincidental, since many epidemiological, clinical, and experimental studies have indicated HCV to be strongly associated with liver steatosis and numerous metabolic derangements. Here, we present an overview of publications that provide clinical evidence of the metabolic effects of HCV and summarize the available data on the pathogenetic mechanisms of this association. It has been shown that HCV infection can induce insulin resistance (IR) in the liver and peripheral tissues through multiple mechanisms. Substantial research has suggested that HCV interferes with insulin signaling both directly and indirectly, inducing the production of several proinflammatory cytokines. HCV replication, assembly, and release from hepatocytes require close interactions with lipid droplets and host lipoproteins. This modulation of lipid metabolism in host cells can induce hepatic steatosis, which is more pronounced in patients with HCV genotype 3. The risk of steatosis depends on several viral factors (including genotype, viral load, and gene mutations) and host features (visceral obesity, type 2 diabetes mellitus, genetic predisposition, medication use, and alcohol consumption). HCV-related IR and steatosis have been shown to have a remarkable clinical impact on the prognosis of HCV infection and quality of life, due to their association with resistance to antiviral therapy, progression of hepatic fibrosis, and development of hepatocellular carcinoma. Finally, HCV-induced IR, oxidative stress, and changes in lipid and iron metabolism lead to glucose intolerance, arterial hypertension, hyperuricemia, and atherosclerosis, resulting in increased cardiovascular mortality. PMID:27047774

  16. Hepatitis C Virus, Insulin Resistance, and Steatosis.

    PubMed

    Kralj, Dominik; Virović Jukić, Lucija; Stojsavljević, Sanja; Duvnjak, Marko; Smolić, Martina; Čurčić, Ines Bilić

    2016-03-28

    Hepatitis C virus (HCV) is one of the main causes of liver disease worldwide. Liver steatosis is a common finding in many hepatic and extrahepatic disorders, the most common being metabolic syndrome (MS). Over time, it has been shown that the frequent coexistence of these two conditions is not coincidental, since many epidemiological, clinical, and experimental studies have indicated HCV to be strongly associated with liver steatosis and numerous metabolic derangements. Here, we present an overview of publications that provide clinical evidence of the metabolic effects of HCV and summarize the available data on the pathogenetic mechanisms of this association. It has been shown that HCV infection can induce insulin resistance (IR) in the liver and peripheral tissues through multiple mechanisms. Substantial research has suggested that HCV interferes with insulin signaling both directly and indirectly, inducing the production of several proinflammatory cytokines. HCV replication, assembly, and release from hepatocytes require close interactions with lipid droplets and host lipoproteins. This modulation of lipid metabolism in host cells can induce hepatic steatosis, which is more pronounced in patients with HCV genotype 3. The risk of steatosis depends on several viral factors (including genotype, viral load, and gene mutations) and host features (visceral obesity, type 2 diabetes mellitus, genetic predisposition, medication use, and alcohol consumption). HCV-related IR and steatosis have been shown to have a remarkable clinical impact on the prognosis of HCV infection and quality of life, due to their association with resistance to antiviral therapy, progression of hepatic fibrosis, and development of hepatocellular carcinoma. Finally, HCV-induced IR, oxidative stress, and changes in lipid and iron metabolism lead to glucose intolerance, arterial hypertension, hyperuricemia, and atherosclerosis, resulting in increased cardiovascular mortality. PMID:27047774

  17. Virus-Specific Cellular Response in Hepatitis C Virus Infection.

    PubMed

    Kaźmierczak, Justyna; Caraballo Cortes, Kamila; Bukowska-Ośko, Iwona; Radkowski, Marek

    2016-04-01

    Studies performed on chimpanzees and humans have revealed that strong, multispecific and sustained CD4(+) and CD8(+) T cell immune responses is a major determinant of hepatitis C virus (HCV) clearance. However, spontaneous elimination of the virus occurs in minority of infected individuals and cellular response directed against HCV antigens is not persistent in individuals with chronic infection. This review presents characteristics of the HCV-specific T cell response in patients with different clinical course of infection, including acute and chronic infection, persons who spontaneously eliminated HCV and non-infected subjects exposed to HCV. Detection of HCV-specific response, especially in non-infected subjects exposed to HCV, may be indicative of HCV prevalence in population and rate of spontaneous viral clearance. Understanding the mechanisms and role of HCV-specific cellular immune response would contribute to better understanding of HCV epidemiology, immunopathogenesis and may help to design an effective vaccine. PMID:26429740

  18. Characterization of duck enteritis virus UL53 gene and glycoprotein K

    PubMed Central

    2011-01-01

    Background Most of the previous research work had focused on the epidemiology and prevention of duck enteritis virus (DEV). Whilst with the development of protocols in molecular biology, nowadays more and more information about the genes of DEV was reported. But little information about DEV UL53 gene and glycoprotein K(gK) was known except our reported data. Results In our paper, the fluorescent quantitative real-time PCR(FQ-RT-PCR) assay and nucleic acid inhibition test were used to study the transcription characteristic of the DEV UL53 gene. Except detecting the mRNA of DEV UL53 gene, the product gK encoded by UL53 gene was detected through the expression kinetics of UL53 gene by the purified rabbit anti-UL53 protein polyclonal antibodies. Western-blotting and indirect immunofluorescence assays were used to detect gK. From the results of these experiments, the UL53 gene and gK were respectively identified as a late gene and a really late protein. On the other hand, the indirect immunofluorescence assay provided another information that the intracellular localization of DEV gK was mainly distributed in cytoplasm. Conclusions By way of conclusions, we conceded that DEV UL53 gene is a really late gene, which is coincident with properties of UL53 homologs from other herpesvirus, such as ILTV(Infectious Laryngotracheitis virus) and HSV-1(Herpes simplex virus type 1). The properties of intracellular localization about gK protein provided a foundation for further functional analysis and further studies will be focused on constructing of the UL53 gene DEV mutant. PMID:21586146

  19. The origin of hepatitis C virus.

    PubMed

    Simmonds, Peter

    2013-01-01

    The origin of hepatitis C virus (HCV) can be conceptualised at several levels. Firstly, origins might refer to its dramatic spread throughout the Western world and developing countries throughout the twentieth century. As a blood-borne virus, this epidemic was fuelled by new parenteral transmission routes associated with medical treatments, immunisation, blood transfusion and more recently injecting drug use. At another level, however, origins might refer to the immediate sources of HCV associated with its pandemic spread, now identified as areas in Central and West sub-Saharan Africa and South and South East Asia where genetically diverse variants of HCV appear to have circulated for hundreds of years. Going back a final step to the actual source of HCV infection in these endemic areas, non-human primates have been long suspected as harbouring viruses related to HCV with potential cross-species transmission of variants corresponding to the 7 main genotypes into humans. Although there is tempting analogy between this and the clearly zoonotic origin of HIV-1 from chimpanzees in Central Africa, no published evidence to date has been obtained for infection of HCV-like viruses in either apes or Old World monkey species. Indeed, a radical re-think of both the host range and host-specificity of hepaciviruses is now required following the very recent findings of a non-primate hepacivirus (NPHV) in horses and potentially in dogs. Further research on a much wider range of mammals is needed to better understand the true genetic diversity of HCV-like viruses and their host ranges in the search for the ultimate origin of HCV in humans. PMID:23463195

  20. DEVELOPMENT OF A MOLECULAR METHOD TO IDENTIFY HEPATITIS E VIRUS

    EPA Science Inventory

    Hepatitis E virus (HEV) is a waterborne emerging pathogen that causes significant illness in the developing world. Thus far, an HEV outbreak has not been reported in the U.S., although a swine variant of the virus is common in Midwestern hogs. Because viruses isolated from two ...

  1. Locally acquired hepatitis E virus infection, El Paso, Texas.

    PubMed

    Amon, Joseph J; Drobeniuc, Jan; Bower, William A; Magaña, Jorge C; Escobedo, Miguel A; Williams, Ian T; Bell, Beth P; Armstrong, Gregory L

    2006-06-01

    Hepatitis E virus (HEV) is an enterically transmitted RNA virus that causes both epidemic and sporadic cases of acute hepatitis. Despite sero-surveys showing antibody to HEV in up to 36% of the US population, acute hepatitis E has been reported among individuals with no history of international travel only three times in the United States. We report a case of apparently locally-acquired hepatitis E that occurred in El Paso, Texas that was 98% similar to a previously isolated HEV found in swine in the United States. Like the three previous cases, a thorough investigation found no conclusive sources of infection. Active case surveillance found no additional cases. PMID:16628579

  2. Type a influenza virus surveillance in free-flying, nonmigratory ducks residing on the eastern shore of Maryland

    USGS Publications Warehouse

    Slemons, R.D.; Hansen, W.R.; Converse, K.A.; Senne, D.A.

    2003-01-01

    Virus surveillance in free-flying, nonmigratory ducks living on the eastern shore of Maryland indicated that influenza A viruses were introduced into the area or that the prevalence of endemic infections increased between July 15 and August 27, 1998. Cloacal swabs collected between May 28 and July 15, 1998, were negative for influenza A virus recovery (0/233), whereas 13.9% (29/209) of swabs collected between August 27 and September 2, 1998, were positive for influenza A virus recovery. Five hemagglutinin subtypes (H2, H3, H6, H9, and H12), six neuraminidase subtypes (N1, N2, N4, N5, N6, and N8), and nine HA-NA combinations were identified among 29 influenza A isolates. Interestingly, 18 of the 29 isolates initially appeared to contain two or more HA and/or NA subtypes. The free-flying, nonmigratory ducks served as excellent sentinels for the early detection of type A influenza viruses in the southern half of the Atlantic Migratory Waterfowl Flyway during the earliest phase of the yearly southern migration.

  3. Type A influenza virus surveillance in free-flying, nonmigratory ducks residing on the eastern shore of Maryland

    USGS Publications Warehouse

    Slemons, R.D.; Hansen, W.R.; Converse, K.A.; Senne, D.A.

    2003-01-01

    Virus surveillance in free-flying, nonmigratory ducks living on the eastern shore of Maryland indicated that influenza A viruses were introduced into the area or that the prevalence of endemic infections increased between July 15 and August 27, 1998. Cloacal swabs collected between May 28 and July 15, 1998, were negative for influenza A virus recovery (0/233), whereas 13.9% (29/209) of swabs collected between August 27 and September 2, 1998, were positive for influenza A virus recovery. Five hemagglutinin subtypes (H2, H3, H6, H9, and H12), six neuraminidase subtypes (N1, N2, N4, N5, N6, and N8), and nine HA-NA combinations were identified among 29 influenza A isolates. Interestingly, 18 of the 29 isolates initially appeared to contain two or more HA and/or NA subtypes. The free-flying, nonmigratory ducks served as excellent sentinels for the early detection of type A influenza viruses in the southern half of the Atlantic Migratory Waterfowl Flyway during the earliest phase of the yearly southern migration.

  4. Genome Analysis of a Tembusu Virus, GX2013H, Isolated from a Cheery Valley Duck in Guangxi, China

    PubMed Central

    Zeng, Tingting; Xie, Liji; Deng, Xianwen; Xie, Zhiqin; Liu, Jiabo; Fan, Qing; Pang, Yaoshan; Luo, Sisi

    2014-01-01

    We report here the complete genome sequence of a duck Tembusu virus (DTMUV) strain, GX2013H, isolated from a duck from Cheery Valley in the Guangxi Province of southern China in 2013. We obtained the strain GX2013H from a Cheery Valley duck with severely decreased egg production and neurological signs. The genome of GX2013H is 10,990 nucleotides (nt) in length and contains a single open reading frame encoding a putative polyprotein of 3,425 amino acids (aa). A comparison of the complete sequence and the deduced amino acid sequence of GX2013H with published sequences of 15 other chicken anemia viruses from China showed that the homologies of the nucleotides are approximately 96.5% to 97.5% and the homologies of the deduced amino acid sequences are approximately 98.9% to 99.3%. This report will help to understand the epidemiology and molecular characteristics of TMUV in Guangxi. PMID:25013132

  5. Expression of the C-terminal ORF2 protein of duck astrovirus for application in a serological test.

    PubMed

    Wang, Xiaoyan; Wang, Yuzhou; Xie, Xiaoyu; Zhang, Bing; Zhang, Dabing

    2011-01-01

    Duck astrovirus (DAstV) is an important pathogen causing duck viral hepatitis (DVH), a highly contagious and fatal disease in young ducklings. To provide an antigen for a diagnostic serum test, the C-terminus of DAstV ORF2 protein was expressed in Escherichia coli. Four positive and 30 negative sera were used to validate the purified ORF2 protein by developing an indirect enzyme-linked immunosorbent assay (ELISA). No cross-reactions were found against other duck pathogens, including duck hepatitis A virus, duck plague herpesvirus, duck reovirus, Newcastle disease virus, and Riemerella anatipestifer 12/19 (63.2%) and 26/51 (51%) sera samples from two flocks of ducks that survived DAstV infections in commercial duck farms were positive for DAstV by this method, respectively. Interestingly, DAstV-specific antibodies were also detected in 12 (28.6%) of 42 sera samples from a different flock without DVH, indicating a wide distribution of subclinical infections caused by DAstV. PMID:20863856

  6. Transcriptional analysis of the innate immune response of ducks to different species-of-origin low pathogenic H7 avian influenza viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Ducks represent an important reservoir for avian influenza (AI) viruses and are partly responsible for the worldwide dissemination of AI. Due to the ability of some low pathogenicity avian influenza viruses (LPAIV) of the hemagglutinin H7 subtype to mutate into a highly pathogenic form o...

  7. Use of genomic interspecies microarray hybridization to detect differentially expressed genes associated with H5N1 avian influenza virus infections in ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Asian H5N1 highly pathogenic avian influenza (HPAI) viruses have changed from producing mild respiratory infections in ducks, to some strains producing severe disease and mortality. The objective of this study was to examine the differences in host response to infection with H5N1 HPAI viruses w...

  8. Characterization of a Novel Reassortant Influenza A Virus (H2N2) from a Domestic Duck in Eastern China

    PubMed Central

    Ma, Mai-Juan; Yang, Xiao-Xian; Qian, Yan-Hua; Zhao, Si-Yan; Hua, Sha; Wang, Tie-Cheng; Chen, Shan-Hui; Ma, Guang-Yuan; Sang, Xiao-Yu; Liu, Lin-Na; Wu, Ai-Ping; Jiang, Tai-Jiao; Gao, Yu-Wei; Gray, Gregory C.; Zhao, Teng; Ling, Xia; Wang, Jing-Lin; Lu, Bing; Qian, Jun; Cao, Wu-Chun

    2014-01-01

    While H2N2 viruses have been sporadically isolated from wild and domestic birds, H2N2 viruses have not been detected among human populations since 1968. Should H2N2 viruses adapt to domestic poultry they may pose a risk of infection to people, as most anyone born after 1968 would likely be susceptible to their infection. We report the isolation of a novel influenza A virus (H2N2) cultured in 2013 from a healthy domestic duck at a live poultry market in Wuxi City, China. Sequence data revealed that the novel H2N2 virus was similar to Eurasian avian lineage avian influenza viruses, the virus had been circulating for ≥ two years among poultry, had an increase in α2,6 binding affinity, and was not highly pathogenic. Approximately 9% of 100 healthy chickens sampled from the same area had elevated antibodies against the H2 antigen. Fortunately, there was sparse serological evidence that the virus was infecting poultry workers or had adapted to infect other mammals. These findings suggest that a novel H2N2 virus has been circulating among domestic poultry in Wuxi City, China and has some has increased human receptor affinity. It seems wise to conduct better surveillance for novel influenza viruses at Chinese live bird markets. PMID:25533850

  9. Hepatitis delta virus: A fascinating and neglected pathogen

    PubMed Central

    Cunha, Celso; Tavanez, João Paulo; Gudima, Severin

    2015-01-01

    Hepatitis delta virus (HDV) is the etiologic agent of the most severe form of virus hepatitis in humans. Sharing some structural and functional properties with plant viroids, the HDV RNA contains a single open reading frame coding for the only virus protein, the Delta antigen. A number of unique features, including ribozyme activity, RNA editing, rolling-circle RNA replication, and redirection for a RNA template of host DNA-dependent RNA polymerase II, make this small pathogen an excellent model to study virus-cell interactions and RNA biology. Treatment options for chronic hepatitis Delta are scarce and ineffective. The disease burden is perhaps largely underestimated making the search for new, specific drugs, targets, and treatment strategies an important public health challenge. In this review we address the main features of virus structure, replication, and interaction with the host. Virus pathogenicity and current treatment options are discussed in the light of recent developments. PMID:26568914

  10. Hepatitis delta virus: A fascinating and neglected pathogen.

    PubMed

    Cunha, Celso; Tavanez, João Paulo; Gudima, Severin

    2015-11-12

    Hepatitis delta virus (HDV) is the etiologic agent of the most severe form of virus hepatitis in humans. Sharing some structural and functional properties with plant viroids, the HDV RNA contains a single open reading frame coding for the only virus protein, the Delta antigen. A number of unique features, including ribozyme activity, RNA editing, rolling-circle RNA replication, and redirection for a RNA template of host DNA-dependent RNA polymerase II, make this small pathogen an excellent model to study virus-cell interactions and RNA biology. Treatment options for chronic hepatitis Delta are scarce and ineffective. The disease burden is perhaps largely underestimated making the search for new, specific drugs, targets, and treatment strategies an important public health challenge. In this review we address the main features of virus structure, replication, and interaction with the host. Virus pathogenicity and current treatment options are discussed in the light of recent developments. PMID:26568914

  11. Hepatitis C virus genetic variability and evolution

    PubMed Central

    Echeverría, Natalia; Moratorio, Gonzalo; Cristina, Juan; Moreno, Pilar

    2015-01-01

    Hepatitis C virus (HCV) has infected over 170 million people worldwide and creates a huge disease burden due to chronic, progressive liver disease. HCV is a single-stranded, positive sense, RNA virus, member of the Flaviviridae family. The high error rate of RNA-dependent RNA polymerase and the pressure exerted by the host immune system, has driven the evolution of HCV into 7 different genotypes and more than 67 subtypes. HCV evolves by means of different mechanisms of genetic variation. On the one hand, its high mutation rates generate the production of a large number of different but closely related viral variants during infection, usually referred to as a quasispecies. The great quasispecies variability of HCV has also therapeutic implications since the continuous generation and selection of resistant or fitter variants within the quasispecies spectrum might allow viruses to escape control by antiviral drugs. On the other hand HCV exploits recombination to ensure its survival. This enormous viral diversity together with some host factors has made it difficult to control viral dispersal. Current treatment options involve pegylated interferon-α and ribavirin as dual therapy or in combination with a direct-acting antiviral drug, depending on the country. Despite all the efforts put into antiviral therapy studies, eradication of the virus or the development of a preventive vaccine has been unsuccessful so far. This review focuses on current available data reported to date on the genetic mechanisms driving the molecular evolution of HCV populations and its relation with the antiviral therapies designed to control HCV infection. PMID:25937861

  12. Epidemiology and prevention of hepatitis B virus infection

    PubMed Central

    Kwon, So Young

    2011-01-01

    Hepatitis B virus (HBV) infection has been a major global cause of morbidity and mortality. The recognition of the problem led to a worldwide effort to reduce transmission of HBV through routine infant vaccination. HBV infection is the most common cause of chronic liver diseases and hepatocellular carcinoma in Korea. After hepatitis B vaccine era, seroprevalence of hepatits B surface antigen is decreasing, particularly in children. Hepatitis B vaccine is remarkably safe and shows high immunogenicity. Universal childhood immunization with three doses of hepatitis B vaccine in the first year of life is a highly effective method for prevention and control of hepatitis B. PMID:21757978

  13. Sofosbuvir treatment and hepatitis C virus infection.

    PubMed

    Nakamura, Masato; Kanda, Tatsuo; Haga, Yuki; Sasaki, Reina; Wu, Shuang; Nakamoto, Shingo; Yasui, Shin; Arai, Makoto; Imazeki, Fumio; Yokosuka, Osamu

    2016-01-28

    Hepatitis C virus (HCV) infection is a serious problem worldwide. The use of interferon-based therapy has made HCV eradication challenging. The recent appearance of direct-acting antiviral agents (DAAs) has changed HCV therapy. Combining the use of DAAs with peginterferon and ribavirin has improved treatment efficacy. Furthermore, the combination of different orally administered DAAs has enabled interferon-free therapy with much higher efficacy and safety. In particular, sofosbuvir, a nucleotide-based NS5B inhibitor, prevents HCV RNA synthesis by acting as a "chain terminator". Treatment with sofosbuvir has attained an extremely high rate of sustained virologic response. The current review summarizes the efficacy and safety of sofosbuvir therapy. PMID:26839641

  14. Sofosbuvir treatment and hepatitis C virus infection

    PubMed Central

    Nakamura, Masato; Kanda, Tatsuo; Haga, Yuki; Sasaki, Reina; Wu, Shuang; Nakamoto, Shingo; Yasui, Shin; Arai, Makoto; Imazeki, Fumio; Yokosuka, Osamu

    2016-01-01

    Hepatitis C virus (HCV) infection is a serious problem worldwide. The use of interferon-based therapy has made HCV eradication challenging. The recent appearance of direct-acting antiviral agents (DAAs) has changed HCV therapy. Combining the use of DAAs with peginterferon and ribavirin has improved treatment efficacy. Furthermore, the combination of different orally administered DAAs has enabled interferon-free therapy with much higher efficacy and safety. In particular, sofosbuvir, a nucleotide-based NS5B inhibitor, prevents HCV RNA synthesis by acting as a “chain terminator”. Treatment with sofosbuvir has attained an extremely high rate of sustained virologic response. The current review summarizes the efficacy and safety of sofosbuvir therapy. PMID:26839641

  15. [Escape mutants of hepatitis B virus].

    PubMed

    Jaramillo, Carlos Mario; Navas, María-Cristina

    2015-04-01

    The hepatitis B virus (HBV) infection is a public health problem worldwide. Considering HBV morbidity and mortality and the economic consequences .of this infection, policies and strategies to control it have been implemented, especially in regions where HBV infection is endemic, with high rates of vertical and horizontal infection. One of these strategies is the development of the recombinant vaccine. A 92% of the countries in the world have implemented the vaccine with a global coverage of 69%. The escape variants of HBV correspond to isolates with mutations in the sequence coding for the "a" determinant; these mutations result in changes in the amino acid sequence of the surface antigen (HBsAg) that prevent neutralization of viral particles by antibodies generated in response to vaccination or infection. The escape variants can infect vaccinated individuals and have been identified in the population of countries with different epidemiological patterns. PMID:26065452

  16. [Laboratory diagnosis of hepatitis C virus infection].

    PubMed

    Huber, K R; Kittl, E; Sebesta, C; Bauer, K

    2000-01-01

    In Austria, the prevalence of hepatitis C virus infections is 0.7% (17). Exclusion of a putative infection as well as diagnosis and continuous monitoring of HCV-disease produce considerable costs for the health system. How many and which patients with HCV infection will acquire life-threatening complications is by far not clear. Also, the causes for viral persistence and liver-complications remain obscure. For certain, complex interactions of viral and immunological mechanisms will determine the individual outcome of the disease (1). These considerations pose decisive demands on clinical diagnostics for HCV infections to be dealt with in detail: methods for qualitative detection of an infection as well as for analysis of subtypes and for quantitative determination of viral copies; monitoring of therapy; estimation of the progress of the disease and/or efficacy of therapy. PMID:11205177

  17. Hepatitis C Virus Hijacks Host Lipid Metabolism

    PubMed Central

    Syed, Gulam H; Amako, Yutaka; Siddiqui, Aleem

    2009-01-01

    Hepatitis C virus (HCV) modulates cellular lipid metabolism to enhance its replication. HCV circulates in the blood in association with lipoproteins. HCV infection is associated with enhanced lipogenesis, reduced secretion and β-oxidation of lipids. HCV-induced imbalance in lipid homeostasis leads to steatosis. Many lipids are crucial for viral life cycle, and inhibitors of cholesterol/fatty acid biosynthetic pathways inhibit viral replication, maturation and secretion. HCV negatively modulates the synthesis and secretion of very low-density lipoproteins (VLDL). The components involved in VLDL assembly are also required for HCV morphogenesis/secretion, suggesting that HCV coopts the VLDL secretory pathway for its own secretion. This review highlights HCV-altered lipid metabolic events that aid in the viral life cycle and ultimately promote liver disease pathogenesis. PMID:19854061

  18. Differences in pathogenicity, response to vaccination, and innate immune responses in different types of ducks infected with a virulent H5N1 highly pathogenic avian influenza virus from Vietnam

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Wild ducks are reservoirs of avian influenza viruses in nature, and usually don’t show signs of disease. However, some Asian lineage H5N1 highly pathogenic avian influenza (HPAI) viruses can cause disease and death in both wild and domestic ducks. The objective of this study was to compare the cli...

  19. Hepatitis B virus infection in Indonesia

    PubMed Central

    Yano, Yoshihiko; Utsumi, Takako; Lusida, Maria Inge; Hayashi, Yoshitake

    2015-01-01

    Approximately 240 million people are chronically infected with hepatitis B virus (HBV), 75% of whom reside in Asia. Approximately 600000 of infected patients die each year due to HBV-related diseases or hepatocellular carcinoma (HCC). The endemicity of hepatitis surface antigen in Indonesia is intermediate to high with a geographical difference. The risk of HBV infection is high in hemodialysis (HD) patients, men having sex with men, and health care workers. Occult HBV infection has been detected in various groups such as blood donors, HD patients, and HIV-infected individuals and children. The most common HBV subgenotype in Indonesia is B3 followed by C1. Various novel subgenotypes of HBV have been identified throughout Indonesia, with the novel HBV subgenotypes C6-C16 and D6 being successfully isolated. Although a number of HBV subgenotypes have been discovered in Indonesia, genotype-related pathogenicity has not yet been elucidated in detail. Therefore, genotype-related differences in the prognosis of liver disease and their effects on treatments need to be determined. A previous study conducted in Indonesia revealed that hepatic steatosis was associated with disease progression. Pre-S2 mutations and mutations at C1638T and T1753V in HBV/B3 have been associated with advanced liver diseases including HCC. However, drug resistance to lamivudine, which is prominent in Indonesia, remains obscure. Although the number of studies on HBV in Indonesia has been increasing, adequate databases on HBV infection are limited. We herein provided an overview of the epidemiology and clinical characteristics of HBV infection in Indonesia. PMID:26478663

  20. Cognitive dysfunction and hepatitis C virus infection

    PubMed Central

    Solinas, Antonio; Piras, Maria Rita; Deplano, Angelo

    2015-01-01

    Cognitive dysfunction in patients with chronic hepatitis C virus (HCV) infection is a distinct form of minimal hepatic encephalopathy (MHE). In fact, the majority of HCV-positive patients, irrespective of the grading of liver fibrosis, display alterations of verbal learning, attention, executive function, and memory when they are evaluated by suitable neuropsychological tests. Similarities between the cognitive dysfunction of HCV patients and MHE of patients with different etiologies are unclear. It is also unknown how the metabolic alterations of advanced liver diseases interact with the HCV-induced cognitive dysfunction, and whether these alterations are reversed by antiviral therapies. HCV replication in the brain may play a role in the pathogenesis of neuroinflammation. HCV-related brain dysfunction may be associated with white matter neuronal loss, alterations of association tracts and perfusion. It is unclear to what extent, in patients with cirrhosis, HCV triggers an irreversible neurodegenerative brain damage. New insights on this issue will be provided by longitudinal studies using the protocols established by the diagnostic and statistical manual of mental disorders fifth edition for cognitive disorders. The domains to be evaluated are complex attention; executive functions; learning and memory; perceptual motor functions; social cognition. These evaluations should be associated with fluorodeoxyglucose positron emission tomography and magnetic resonance imaging (MRI) protocols for major cognitive disorders including magnetic resonance spectroscopy, diffusion tensor imaging, magnetic resonance perfusion, and functional MRI. Also, the characteristics of portal hypertension, including the extent of liver blood flow and the type of portal shunts, should be evaluated. PMID:25954475

  1. Expression and characterization of duck enteritis virus gI gene

    PubMed Central

    2011-01-01

    Background At present, alphaherpesviruses gI gene and its encoding protein have been extensively studied. It is likely that gI protein and its homolog play similar roles in virions direct cell-to-cell spread of alphaherpesviruses. But, little is known about the characteristics of DEV gI gene. In this study, we expressed and presented the basic properties of the DEV gI protein. Results The special 1221-bp fragment containing complete open reading frame(ORF) of duck enteritis virus(DEV) gI gene was extracted from plasmid pMD18-T-gI, and then cloned into prokaryotic expression vector pET-32a(+), resulting in pET-32a(+)-gI. After being confirmed by PCR, restriction endonuclease digestion and sequencing, pET-32a(+)-gI was transformed into E.coli BL21(DE3) competent cells for overexpression. DEV gI gene was successfully expressed by the addition of isopropyl-β-D-thiogalactopyranoside(IPTG). SDS-PAGE showed that the recombinant protein His6-tagged gI molecular weight was about 61 kDa. Subsequently, the expressed product was applied to generate specific antibody against gI protein. The specificity of the rabbit immuneserum was confirmed by its ability to react with the recombinant protein His6-tagged gI. In addition, real time-PCR was used to determine the the levels of the mRNA transcripts of gI gene, the results showed that the DEV gI gene was transcribed most abundantly during the late phase of infection. Furthermore, indirect immunofluorescence(IIF) was established to study the gI protein expression and localization in DEV-infected duck embryo fibroblasts (DEFs), the results confirmed that the protein was expressed and located in the cytoplasm of the infected cells, intensively. Conclusions The recombinant prokaryotic expression vector of DEV gI gene was constructed successfully. The gI protein was successfully expressed by E.coli BL21(DE3) and maintained its antigenicity very well. The basic information of the transcription and intracellular localization of gI gene

  2. Inhibition of hepatitis B virus gene expression & replication by crude destruxins from Metarhizium anisopliae var. dcjhyium

    PubMed Central

    Dong, Cong; Yu, Jiuru; Zhu, Ying; Dong, Changjin

    2013-01-01

    Background & objectives: Destruxin A, destruxin B and destruxin E isolated from entomopathogenic fungus Metarhizium anisopliae showed a strong suppressive effect on the replication of hepatitis B virus (HBV) in human hepatoma cells. In this study, the anti-HBV effects of the crude destruxins extracted from M. anisopliae var. dcjhyium were detected both in vitro and in vivo. Methods: HepG2.2.15 cells were cultured to observe the inhibitory effects of the crude destruxins on the gene expression and replication of HBV by radioimmunoassay detection and real-time quantitative PCR. In vivo, duck HBV (DHBV)-infected ducks were treated with the crude destruxins at 2.0, 4.0, 6.0 μg/kg once a day for 15 days, DHBV DNA was examined by real-time quantitative PCR. Results: The crude destruxins suppressed the replication of HBV-DNA and the production of HBsAg and HBeAg with IC50 of about 1.2 and 1.4 μg/ml. Transcript of viral mRNA was significantly suppressed by the crude destruxins in HepG2.2.15 cells. In vivo, the duck serum DHBV-DNA levels were markedly reduced in the group of the crude destruxins. Interpretation & conclusions: The crude destruxins inhibited the gene expression and replication of HBV both in vitro and in vivo, and their anti-HBV effect was stronger than that with destruxin B. Our results indicate that the crude destruxins from M.anisopliae var. dcjhyium may be potential antivirus agents. Further studies need to be done to confirm these findings. PMID:24521644

  3. IFNL4 affects clearance of hepatitis C virus

    Cancer.gov

    Scientists have discovered a new human interferon gene, Interferon Lambda 4 (IFNL4), that affects clearance of the hepatitis C virus. They also identified an inherited genetic variant within IFNL4 that predicts how people respond to treatment for hepatit

  4. NIH Scientists Shed Light on Mystery Surrounding Hepatitis B Virus

    MedlinePlus

    ... Research 2013 January 2013 (historical) NIH Scientists Shed Light on Mystery Surrounding Hepatitis B Virus Discovery Is ... the University of Oxford, U.K., have shed light on a long-standing enigma about the structure ...

  5. Characteristics of an outpatient chronic hepatitis B virus infection cohort

    PubMed Central

    de Assis, Danyenne Rejane; Tenore, Simone de Barros; Pinho, João Renato Rebello; Lewi, David Salomão; Ferreira, Paulo Roberto Abrão

    2015-01-01

    ABSTRACT Objective: To characterize a chronic hepatitis B cohort based on initial and follow-up clinical evaluations. Methods: A retrospective and descriptive analysis of clinical and laboratory data from chronic HBsAg adult carriers, without HIV, unexposed to treatment, with at least two outpatient visits, between February 2006 and November 2012. Fisher´s exact test, χ², Wilcoxon, Spearman, multiple comparisons and Kappa tests were applied, the level of significance adopted was 5%, with a 95% confidence interval. Results: 175 patients with mean age of 42.95±12.53 years were included: 93 (53.1%) were men, 152 (86.9%) were negative for hepatitis B e-antigen (HBeAg), 3 (1.7%) had hepatitis C coinfection, 15 (8.6%) had cirrhosis, and 2 (1.1%) had hepatocellular carcinoma. Genotype A predominated. Sixty-six patients (37.7%) had active hepatitis, 6 (3.4%) presented immune tolerance, and 38 (21.7%) were inactive carriers. Exacerbations and/or viral breakthrough were detected in 16 patients (9.1%). In 32 patients (18.3%), hepatitis B virus DNA remained persistently elevated and alanine aminotransferase levels were normal, whereas in 17 (9.7%), there was low hepatitis B virus DNA and alterated alanine aminotransferase. If only initial alanine aminotransferase and hepatitis B virus DNA values were considered, 15 cases of active hepatitis would not have been detected. Advanced fibrosis was more common in HBeAg-positive patients, and it was significantly associated with transaminases, hepatitis B virus DNA, and age. Conclusion: Many patients had active hepatitis, but almost 25%, who were HBeAg non-reactive, were only identified because of combined analyses of the hepatitis B virus DNA and transaminases levels, sometimes associated with histological data, after clinical follow-up. PMID:26154539

  6. Seroprevalence of hepatitis B and C virus in two institutions caring for mentally handicapped adults.

    PubMed Central

    Cramp, M E; Grundy, H C; Perinpanayagam, R M; Barnado, D E

    1996-01-01

    Hepatitis B virus infection is common in institutions caring for the mentally handicapped. Hepatitis B virus and hepatitis C virus share routes of transmission but the prevalence of hepatitis C virus infection in this population is unknown. We have tested 101 patients from two institutions in South-East England caring for adults with mental handicap for the presence of hepatitis C antibody, hepatitis B core antibody, and if necessary hepatitis B surface antigen. None tested positive for hepatitis C antibody, but 43 had hepatitis B core antibody of whom 14 were chronic carriers positive for hepatitis B surface antigen. Unlike hepatitis B virus, hepatitis C virus infection appears to be uncommon in UK institutions. PMID:8774540

  7. Pathobiology of avian influenza in domestic ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Domestic ducks are an important source of food and income in many parts of the world. The susceptibility of domestic ducks to avian influenza (AI) viruses varies depending on many factors, including the species and the age of the ducks, the virus strain, and management practices. Although wild wat...

  8. Tembusu-Related Flavivirus in Ducks, Thailand

    PubMed Central

    Thontiravong, Aunyaratana; Ninvilai, Patchareeporn; Tunterak, Wikanda; Nonthabenjawan, Nutthawan; Chaiyavong, Supassma; Angkabkingkaew, Kingkarn; Mungkundar, Chatthapon; Phuengpho, Woranuch; Oraveerakul, Kanisak

    2015-01-01

    Since 2013, outbreaks of disease caused by duck Tembusu virus (DTMUV) have been observed in layer and broiler duck farms in Thailand. The virus is closely related to Chinese DTMUVs and belongs to the Ntaya group of mosquitoborne flaviviruses. These findings represent the emergence of DTMUV in ducks in Thailand. PMID:26584133

  9. Advanced Molecular Surveillance of Hepatitis C Virus

    PubMed Central

    Gonçalves Rossi, Livia Maria; Escobar-Gutierrez, Alejandro; Rahal, Paula

    2015-01-01

    Hepatitis C virus (HCV) infection is an important public health problem worldwide. HCV exploits complex molecular mechanisms, which result in a high degree of intrahost genetic heterogeneity. This high degree of variability represents a challenge for the accurate establishment of genetic relatedness between cases and complicates the identification of sources of infection. Tracking HCV infections is crucial for the elucidation of routes of transmission in a variety of settings. Therefore, implementation of HCV advanced molecular surveillance (AMS) is essential for disease control. Accounting for virulence is also important for HCV AMS and both viral and host factors contribute to the disease outcome. Therefore, HCV AMS requires the incorporation of host factors as an integral component of the algorithms used to monitor disease occurrence. Importantly, implementation of comprehensive global databases and data mining are also needed for the proper study of the mechanisms responsible for HCV transmission. Here, we review molecular aspects associated with HCV transmission, as well as the most recent technological advances used for virus and host characterization. Additionally, the cornerstone discoveries that have defined the pathway for viral characterization are presented and the importance of implementing advanced HCV molecular surveillance is highlighted. PMID:25781918

  10. Hepatitis C virus-induced hepatocellular carcinoma

    PubMed Central

    Goossens, Nicolas

    2015-01-01

    Hepatitis C virus (HCV) is a leading etiology of hepatocellular carcinoma (HCC). The interaction of HCV with its human host is complex and multilayered; stemming in part from the fact that HCV is a RNA virus with no ability to integrate in the host's genome. Direct and indirect mechanisms of HCV-induced HCC include activation of multiple host pathways such as liver fibrogenic pathways, cellular and survival pathways, interaction with the immune and metabolic systems. Host factors also play a major role in HCV-induced HCC as evidenced by genomic studies identifying polymorphisms in immune, metabolic, and growth signaling systems associated with increased risk of HCC. Despite highly effective direct-acting antiviral agents, the morbidity and incidence of liver-related complications of HCV, including HCC, is likely to persist in the near future. Clinical markers to selectively identify HCV subjects at higher risk of developing HCC have been reported however they require further validation, especially in subjects who have experienced sustained virological response. Molecular biomarkers allowing further refinement of HCC risk are starting to be implemented in clinical platforms, allowing objective stratification of risk and leading to individualized therapy and surveillance for HCV individuals. Another role for molecular biomarker-based stratification could be enrichment of HCC chemoprevention clinical trials leading to smaller sample size, shorter trial duration, and reduced costs. PMID:26157746

  11. Vasculitis as a Presenting Manifestation of Chronic Hepatitis B Virus Infection: A Case Report

    PubMed Central

    Singh, Harpreet; Sukhija, Gagandeep; Kaur, Parminder; Govil, Nikhil

    2016-01-01

    Hepatitis B virus is responsible for causing hepatic complications like acute and chronic hepatitis, cirrhosis and hepatocellular carcinoma along with some uncommon immune mediated extrahepatic manifestations. Vasculitis remains an uncommon extrahepatic complication of hepatitis B virus infection. Herein we report a case of hepatitis B infection that presented with leucocytoclastic vasculitis as an initial manifestation and managed successfully with entacavir therapy. PMID:27042512

  12. Hepatitis D virus infection, replication and cross-talk with the hepatitis B virus

    PubMed Central

    Huang, Chi-Ruei; Lo, Szecheng John

    2014-01-01

    Viral hepatitis remains a worldwide public health problem. The hepatitis D virus (HDV) must either coinfect or superinfect with the hepatitis B virus (HBV). HDV contains a small RNA genome (approximately 1.7 kb) with a single open reading frame (ORF) and requires HBV supplying surface antigens (HBsAgs) to assemble a new HDV virion. During HDV replication, two isoforms of a delta antigen, a small delta antigen (SDAg) and a large delta antigen (LDAg), are produced from the same ORF of the HDV genome. The SDAg is required for HDV replication, whereas the interaction of LDAg with HBsAgs is crucial for packaging of HDV RNA. Various clinical outcomes of HBV/HDV dual infection have been reported, but the molecular interaction between HBV and HDV is poorly understood, especially regarding how HBV and HDV compete with HBsAgs for assembling virions. In this paper, we review the role of endoplasmic reticulum stress induced by HBsAgs and the molecular pathway involved in their promotion of LDAg nuclear export. Because the nuclear sublocalization and export of LDAg is regulated by posttranslational modifications (PTMs), including acetylation, phosphorylation, and isoprenylation, we also summarize the relationship among HBsAg-induced endoplasmic reticulum stress signaling, LDAg PTMs, and nuclear export mechanisms in this review. PMID:25356023

  13. Immune-related gene expression in response to H11N9 low pathogenic avian influenza virus infection in chicken and Pekin duck peripheral blood mononuclear cells.

    PubMed

    Adams, Sean C; Xing, Zheng; Li, Jinling; Cardona, Carol J

    2009-05-01

    The duck and chicken are important hosts of avian influenza virus (AIV) with distinctive responses to infection. Frequently, AIV infections in ducks are asymptomatic and long-lasting in contrast to the clinically apparent and transient infections observed in chickens. These differences may be due in part to the host response to AIV infection. Using real-time quantitative PCR, we examined the expression of immune-related genes in response to low pathogenic AIV H11N9 infection in peripheral blood mononuclear cells (PBMC) isolated from the blood of chickens and Pekin ducks. While chicken PBMC expressed IL-1beta and IL-6 at high levels similar to mammalian species, duck PBMC expression levels were minimal or unchanged. Similarly, duck IFN-beta expression was nearly unaffected, whereas chicken expression was highly upregulated. Chicken IFN-gamma was expressed to higher levels than duck IFN-gamma, while IFN-alpha was expressed similarly by both species. IL-2 was elevated early in infection in duck PBMC, but returned to baseline levels by the end of the experiment; in contrast, IL-2 was weakly induced in chicken PBMC at late time points. TLR-7 and MHC class I molecule expressions were conserved between species, whereas duck MHC class II expression was downregulated and chicken expression was unchanged. These results show distinct PBMC expression patterns of pro-inflammatory cytokines and IFNs between species. The differences in pro-inflammatory cytokine and IFN expression reflect the asymptomatic and lasting infection observed in ducks and the tendency towards clinical signs and rapid clearance seen in chickens. These results highlight important differences in the host response to AIV of two species thought to be critical in the genesis and maintenance of epidemic strains of AIV. PMID:19250679

  14. Pathogenicity and tissue tropism of currently circulating highly pathogenic avian influenza A virus (H5N1; clade 2.3.2) in tufted ducks (Aythya fuligula).

    PubMed

    Bröjer, Caroline; van Amerongen, Geert; van de Bildt, Marco; van Run, Peter; Osterhaus, Albert; Gavier-Widén, Dolores; Kuiken, Thijs

    2015-11-18

    Reports describing the isolation of highly pathogenic avian influenza (HPAI) virus (H5N1) clade 2.3.2 in feces from apparently healthy wild birds and the seemingly lower pathogenicity of this clade compared to clade 2.2 in several experimentally infected species, caused concern that the new clade might be maintained in the wild bird population. To investigate whether the pathogenicity of a clade 2.3.2 virus was lower than that of clades previously occurring in free-living wild birds in Europe, four tufted ducks were inoculated with influenza A/duck/HongKong/1091/2011 (H5N1) clade 2.3.2 virus. The ducks were monitored and sampled for virus excretion daily during 4 days, followed by pathologic, immunohistochemical, and virological investigations. The virus produced severe disease as evidenced by clinical signs, presence of marked lesions and abundant viral antigen in several tissues, especially the central nervous system. The study shows that HPAI-H5N1 virus clade 2.3.2 is highly pathogenic for tufted ducks and thus, they are unlikely to maintain this clade in the free-living population or serve as long-distance vectors. PMID:26441012

  15. Recombinant duck enteritis viruses expressing major structural proteins of the infectious bronchitis virus provide protection against infectious bronchitis in chickens.

    PubMed

    Li, Huixin; Wang, Yulong; Han, Zongxi; Wang, Yu; Liang, Shulin; Jiang, Lu; Hu, Yonghao; Kong, Xiangang; Liu, Shengwang

    2016-06-01

    To design an alternative vaccine for control of infectious bronchitis in chickens, three recombinant duck enteritis viruses (rDEVs) expressing the N, S, or S1 protein of infectious bronchitis virus (IBV) were constructed using conventional homologous recombination methods, and were designated as rDEV-N, rDEV-S, and rDEV-S1, respectively. Chickens were divided into five vaccinated groups, which were each immunized with one of the rDEVs, covalent vaccination with rDEV-N & rDEV-S, or covalent vaccination with rDEV-N & rDEV-S1, and a control group. An antibody response against IBV was detectable and the ratio of CD4(+)/CD8(+) T-lymphocytes decreased at 7 days post-vaccination in each vaccinated group, suggesting that humoral and cellular responses were elicited in each group as early as 7 days post-immunization. After challenge with a homologous virulent IBV strain at 21 days post-immunization, vaccinated groups showed significant differences in the percentage of birds with clinical signs, as compared to the control group (p < 0.01), as the two covalent-vaccination groups and the rDEV-S group provided better protection than the rDEV-N- or rDEV-S1-vaccinated group. There was less viral shedding in the rDEV-N & rDEV-S- (2/10) and rDEV-N & rDEV-S1- (2/10) vaccinated groups than the other three vaccinated groups. Based on the clinical signs, viral shedding, and mortality rates, rDEV-N & rDEV-S1 covalent vaccination conferred better protection than use of any of the single rDEVs. PMID:26946113

  16. Mutations in core nucleotide sequence of hepatitis B virus correlate with fulminant and severe hepatitis.

    PubMed Central

    Ehata, T; Omata, M; Chuang, W L; Yokosuka, O; Ito, Y; Hosoda, K; Ohto, M

    1993-01-01

    Infection with hepatitis B virus leads to a wide spectrum of liver injury, including self-limited acute hepatitis, fulminant hepatitis, and chronic hepatitis with progression to cirrhosis or acute exacerbation to liver failure, as well as an asymptomatic chronic carrier state. Several studies have suggested that the hepatitis B core antigen could be an immunological target of cytotoxic T lymphocytes. To investigate the reason why the extreme immunological attack occurred in fulminant hepatitis and severe exacerbation patients, the entire precore and core region of hepatitis B virus DNA was sequenced in 24 subjects (5 fulminant, 10 severe fatal exacerbation, and 9 self-limited acute hepatitis patients). No significant change in the nucleotide sequence and deduced amino acid residue was noted in the nine self-limited acute hepatitis patients. In contrast, clustering changes in a small segment of 16 amino acids (codon 84-99 from the start of the core gene) in all seven adr subtype infected fulminant and severe exacerbation patients was found. A different segment with clustering substitutions (codon 48-60) was also found in seven of eight adw subtype infected fulminant and severe exacerbation patients. Of the 15 patients, 2 lacked precore stop mutation which was previously reported to be associated with fulminant hepatitis. These data suggest that these core regions with mutations may play an important role in the pathogenesis of hepatitis B viral disease, and such mutations are related to severe liver damage. Images PMID:8450049

  17. Effect of intranasal immunization with inactivated avian influenza virus on local and systemic immune responses in ducks.

    PubMed

    Kang, H; Wang, H; Yu, Q; Yang, Q

    2012-05-01

    To evaluate the effects of co-administration of inactivated avian influenza H9N2 virus and adjuvants in waterfowls, 10-d-old ducks were immunized intranasally with inactivated avian influenza virus (IAIV) combined with CpG DNA and sodium cholate. Immunoglobulin A and IgG antibody levels in throat and tracheal tissues increased significantly, as did specific IgA and IgG antibody levels in the serum after intranasal immunization with IAIV combined with CpG DNA and sodium cholate, compared with immunization with IAIV only. Furthermore, enhanced hemagglutination inhibition titers were also detected in serum samples taken between the third and seventh weeks after immunization with IAIV and both adjuvants compared with IAIV alone. The expression of IL-2 and IL-6 in tracheal and lung tissues increased significantly in the early period after booster immunization. However, the enhancement induced by a single adjuvant was insignificant, and no significant change was detected in the antibody titers or cytokine levels between the ducks that received IAIV alone or saline. In the viral challenge study, prior administration of both CpG DNA and sodium cholate with IAIV reduced the viral titers in the oropharynx and cloaca swabs. Our study suggests that the combination of CpG DNA and sodium cholate could be beneficial to immunization with inactivated H9N2 virus by enhancing the local and systemic immune responses. PMID:22499863

  18. Characterization of a novel highly pathogenic H5N2 avian influenza virus isolated from a duck in eastern China.

    PubMed

    Wu, Haibo; Peng, Xiaorong; Xu, Lihua; Jin, Changzhong; Cheng, Linfang; Lu, Xiangyun; Xie, Tiansheng; Yao, Hangping; Wu, Nanping

    2014-12-01

    During surveillance for avian influenza viruses (AIVs) in live-poultry markets (LPMs) in eastern China in 2013, one H5N2 AIV was isolated from a duck. Phylogenetic analysis showed that the hemagglutinin of this strain belongs to clade 2.3.4 and received its genes from H5, H3 and H6 AIVs of poultry in China. The virulence of this strain was examined in chickens and mice, and it was found to be highly pathogenic in chickens but demonstrated moderate pathogenicity in mice. These results suggest that active surveillance of AIVs in LPMs should be used in an early warning system for avian influenza outbreaks. PMID:25091744

  19. [Epidemiology of hepatitis E virus infection in Spain].

    PubMed

    Echevarría, José Manuel; Fogeda, Marta; Avellón, Ana

    2015-04-01

    The general features of the epidemiology and ecology of hepatitis E virus in Spain are already known after 20 years of investigations. Genotype 3 strains, mainly from sub-genotype 3f, circulated among swine livestock and certain wild mammals, and would be sporadically transmitted to humans through direct contact with the reservoirs or by consumption of foods derived from them. Bivalve shellfish contaminated by hepatitis E virus from sewage could also play a role in transmission. Although the interpretation of results from seroprevalence studies in low endemic settings is still controversial, antibody to hepatitis E virus displays an overall prevalence less than 10% among the population of Spain, increasing significantly with age. From the, approximately, 150 cases of acute hepatitis E recorded in the international literature, males older than 40 years, suffering a mild, locally acquired disease predominate. In addition, hepatitis E might be more frequent in the North of the country than in other regions. Although the disease does not usually have a great clinical relevance, the occasional finding of cases of fulminant hepatitis, and of ribavirin-resistant, chronic hepatitis E virus infections among the immunocompromised would recommend the surveillance of the infection by the public health authority and a better implementation of specific diagnostic procedures in clinical laboratories. PMID:24447919

  20. Indocyanine green: A test of hepatic function and a measure of plasma volume in the duck

    USGS Publications Warehouse

    Patton, J.F.

    1978-01-01

    1. 1. The exponential removal of ICG from the plasma by the mallard duck liver made possible the measurement of fractional dye clearance (K), plasma volume (PV) and plasma clearance (PC). 2. 2. Values obtained for K (14.9%/min), PV (39.2 ml/kg) and PC (5.8 ml/min per kg) agreed with those obtained by other techniques used in a number of species. 3. 3. Sex did not affect the removal of ICG by the liver. However, increases in K, PV and PC were noted in hen mallards in laying condition. 4. 4. The data should prove useful as baseline values for physiological and pathological studies on the avian liver

  1. Hepatitis E virus is the leading cause of acute viral hepatitis in Lothian, Scotland.

    PubMed

    Kokki, I; Smith, D; Simmonds, P; Ramalingam, S; Wellington, L; Willocks, L; Johannessen, I; Harvala, H

    2016-03-01

    Acute viral hepatitis affects all ages worldwide. Hepatitis E virus (HEV) is increasingly recognized as a major cause of acute hepatitis in Europe. Because knowledge of its characteristics is limited, we conducted a retrospective study to outline demographic and clinical features of acute HEV in comparison to hepatitis A, B and C in Lothian over 28 months (January 2012 to April 2014). A total of 3204 blood samples from patients with suspected acute hepatitis were screened for hepatitis A, B and C virus; 913 of these samples were also screened for HEV. Demographic and clinical information on patients with positive samples was gathered from electronic patient records. Confirmed HEV samples were genotyped. Of 82 patients with confirmed viral hepatitis, 48 (59%) had acute HEV. These patients were older than those infected by hepatitis A, B or C viruses, were more often male and typically presented with jaundice, nausea, vomiting and/or malaise. Most HEV cases (70%) had eaten pork or game meat in the few months before infection, and 14 HEV patients (29%) had a recent history of foreign travel. The majority of samples were HEV genotype 3 (27/30, 90%); three were genotype 1. Acute HEV infection is currently the predominant cause of acute viral hepatitis in Lothian and presents clinically in older men. Most of these infections are autochthonous, and further studies confirming the sources of infection (i.e. food or blood transfusion) are required. PMID:26904201

  2. Hepatitis E virus is the leading cause of acute viral hepatitis in Lothian, Scotland

    PubMed Central

    Kokki, I.; Smith, D.; Simmonds, P.; Ramalingam, S.; Wellington, L.; Willocks, L.; Johannessen, I.; Harvala, H.

    2015-01-01

    Acute viral hepatitis affects all ages worldwide. Hepatitis E virus (HEV) is increasingly recognized as a major cause of acute hepatitis in Europe. Because knowledge of its characteristics is limited, we conducted a retrospective study to outline demographic and clinical features of acute HEV in comparison to hepatitis A, B and C in Lothian over 28 months (January 2012 to April 2014). A total of 3204 blood samples from patients with suspected acute hepatitis were screened for hepatitis A, B and C virus; 913 of these samples were also screened for HEV. Demographic and clinical information on patients with positive samples was gathered from electronic patient records. Confirmed HEV samples were genotyped. Of 82 patients with confirmed viral hepatitis, 48 (59%) had acute HEV. These patients were older than those infected by hepatitis A, B or C viruses, were more often male and typically presented with jaundice, nausea, vomiting and/or malaise. Most HEV cases (70%) had eaten pork or game meat in the few months before infection, and 14 HEV patients (29%) had a recent history of foreign travel. The majority of samples were HEV genotype 3 (27/30, 90%); three were genotype 1. Acute HEV infection is currently the predominant cause of acute viral hepatitis in Lothian and presents clinically in older men. Most of these infections are autochthonous, and further studies confirming the sources of infection (i.e. food or blood transfusion) are required. PMID:26904201

  3. Phenotypic and Genetic Characterization of Avian Influenza H5N2 Viruses with Intra- and Inter-Duck Variations in Taiwan

    PubMed Central

    Li, Yao-Tsun; Lai, Ching-Yu; Kao, Chuan-Liang; Yang, Chinglai; Wang, Won-Bo; King, Chwan-Chuen

    2015-01-01

    Background Human infections with avian influenza viruses (AIVs) have frequently raised global concerns of emerging, interspecies-transmissible viruses with pandemic potential. Waterfowl, the predominant reservoir of influenza viruses in nature, harbor precursors of different genetic lineages that have contributed to novel pandemic influenza viruses in the past. Methods Two duck influenza H5N2 viruses, DV518 and DV413, isolated through virological surveillance at a live-poultry market in Taiwan, showed phylogenetic relatedness but exhibited different replication capabilities in mammalian Madin-Darby Canine Kidney (MDCK) cells. This study characterizes the replication properties of the two duck H5N2 viruses and the determinants involved. Results The DV518 virus replicated more efficiently than DV413 in both MDCK and chicken DF1 cells. Interestingly, the infection of MDCK cells by DV518 formed heterogeneous plaques with great differences in size [large (L) and small (S)], and the two viral strains (p518-L and p518-S) obtained from plaque purification exhibited distinguishable replication kinetics in MDCK cells. Nonetheless, both plaque-purified DV518 strains still maintained their growth advantages over the plaque-purified p413 strain. Moreover, three amino acid substitutions in PA (P224S), PB2 (E72D), and M1 (A128T) were identified in intra-duck variations (p518-L vs p518-S), whereas other changes in HA (N170D), NA (I56T), and NP (Y289H) were present in inter-duck variations (DV518 vs DV413). Both p518-L and p518-S strains had the N170D substitution in HA, which might be related to their greater binding to MDCK cells. Additionally, polymerase activity assays on 293T cells demonstrated the role of vRNP in modulating the replication capability of the duck p518-L viruses in mammalian cells. Conclusion These results demonstrate that intra-host phenotypic variation occurs even within an individual duck. In view of recent human infections by low pathogenic AIVs, this study

  4. Epidemiology of hepatitis C virus in Iran

    PubMed Central

    Taherkhani, Reza; Farshadpour, Fatemeh

    2015-01-01

    In Iran, the prevalence of hepatitis C virus (HCV) infection is relatively low according to the population-based epidemiological studies. However, the epidemiology of HCV is changing and the rate of HCV infection is increasing due to the growth in the number of injecting drug users in the society. In addition, a shift has occurred in the distribution pattern of HCV genotypes among HCV-infected patients in Iran. Genotype 1a is the most prevalent genotype in Iran, but in recent years, an increase in the frequency of 3a and a decrease in 1a and 1b have been reported. These variations in the epidemiology of HCV reflect differences in the routes of transmission, status of public health, lifestyles, and risk factors in different groups and geographic regions of Iran. Health policy makers should consider these differences to establish better strategies for control and prevention of HCV infection. Therefore, this review was conducted to present a clear view regarding the current epidemiology of HCV infection in Iran. PMID:26478671

  5. Medicinal plants against hepatitis C virus

    PubMed Central

    Ashfaq, Usman A; Idrees, Sobia

    2014-01-01

    Hepatitis C virus (HCV) is a global health concern which is responsible for most of the liver diseases. Currently, there is no vaccine available for prevention of HCV infection due to the high degree of strain variation. The current standard of care is a combination of pegylated interferon α with ribavirin and boceprevir/telaprevir. This treatment was partially effective and had significant side effects. Hence, there is a need to develop new antiviral agents that interfere with different stages of the HCV life cycle. Recent advances in the understanding of both the cellular and molecular mechanisms of HCV replication have provided the basis for novel therapeutic strategies. Several hundred plant species and their phyto-constituents have been isolated for screening against HCV, and some have been shown to have great medicinal value in preventing and/or ameliorating viral diseases in pre-clinical and clinical trials. This review summarizes medicinal plants and their phytochemicals which inhibit different stages of HCV life cycle and discuss their potential use in HCV therapy. PMID:24659884

  6. Hepatitis C virus genotypes in Myanmar.

    PubMed

    Win, Nan Nwe; Kanda, Tatsuo; Nakamoto, Shingo; Yokosuka, Osamu; Shirasawa, Hiroshi

    2016-07-21

    Myanmar is adjacent to India, Bangladesh, Thailand, Laos and China. In Myanmar, the prevalence of hepatitis C virus (HCV) infection is 2%, and HCV infection accounts for 25% of hepatocellular carcinoma. In this study, we reviewed the prevalence of HCV genotypes in Myanmar. HCV genotypes 1, 3 and 6 were observed in volunteer blood donors in and around the Myanmar city of Yangon. Although there are several reports of HCV genotype 6 and its variants in Myanmar, the distribution of the HCV genotypes has not been well documented in areas other than Yangon. Previous studies showed that treatment with peginterferon and a weight-based dose of ribavirin for 24 or 48 wk could lead to an 80%-100% sustained virological response (SVR) rates in Myanmar. Current interferon-free treatments could lead to higher SVR rates (90%-95%) in patients infected with almost all HCV genotypes other than HCV genotype 3. In an era of heavy reliance on direct-acting antivirals against HCV, there is an increasing need to measure HCV genotypes, and this need will also increase specifically in Myanmar. Current available information of HCV genotypes were mostly from Yangon and other countries than Myanmar. The prevalence of HCV genotypes in Myanmar should be determined. PMID:27468202

  7. Hepatitis B virus: the genotype E puzzle.

    PubMed

    Andernach, Iris E; Hübschen, Judith M; Muller, Claude P

    2009-07-01

    Hepatitis B virus (HBV) is highly endemic throughout sub-Saharan Africa. One of the two genotypes A and E dominates in most countries. With several subgenotypes and variants, genotype A is more diverse in Africa (4.00%) than in the rest of the world (2.96%), suggesting an African origin and a long history on the continent. Despite the African slave trade, genotype E has only sporadically been found within the Americas, indicating that this genotype was introduced only during the past 200 years into the general African population. A short history for this genotype in Africa is also supported by its conspicuously low genetic diversity (1.75%), which contrasts, however, with its excessively high HBsAg prevalence and its extensive spread throughout the vast West-African genotype E crescent. We discuss the spread and routes of transmission of genotype E and suggest that the distribution and current high prevalence levels of HBV (genotype E) in Africa are the result of the extensive use of unsafe needles, potentially solving the current African genotype E puzzle and shedding new light on the high HBV prevalence in Africa. PMID:19475565

  8. Hepatitis C virus: Virology, diagnosis and treatment

    PubMed Central

    Li, Hui-Chun; Lo, Shih-Yen

    2015-01-01

    More than twenty years of study has provided a better understanding of hepatitis C virus (HCV) life cycle, including the general properties of viral RNA and proteins. This effort facilitates the development of sensitive diagnostic tools and effective antiviral treatments. At present, serologic screening test is recommended to perform on individuals in the high risk groups and nucleic acid tests are recommended to confirm the active HCV infections. Quantization and genotyping of HCV RNAs are important to determine the optimal duration of anti-viral therapy and predict the likelihood of response. In the early 2000s, pegylated interferon plus ribavirin became the standard anti-HCV treatment. However, this therapy is not ideal. To 2014, boceprevir, telaprevir, simeprevir, sofosbuvir and Harvoni are approved by Food and Drug Administration for the treat of HCV infections. It is likely that the new all-oral, interferon-free, pan-genotyping anti-HCV therapy will be available within the next few years. Majority of HCV infections will be cured by these anti-viral treatments. However, not all patients are expected to be cured due to viral resistance and the high cost of antiviral treatments. Thus, an efficient prophylactic vaccine will be the next challenge in the fight against HCV infection. PMID:26052383

  9. Oncogenic Potential of Hepatitis C Virus Proteins

    PubMed Central

    Banerjee, Arup; Ray, Ratna B.; Ray, Ranjit

    2010-01-01

    Chronic hepatitis C virus (HCV) infection is a major risk factor for liver disease progression, and may lead to cirrhosis and hepatocellular carcinoma (HCC). The HCV genome contains a single-stranded positive sense RNA with a cytoplasmic lifecycle. HCV proteins interact with many host-cell factors and are involved in a wide range of activities, including cell cycle regulation, transcriptional regulation, cell proliferation, apoptosis, lipid metabolism, and cell growth promotion. Increasing experimental evidences suggest that HCV contributes to HCC by modulating pathways that may promote malignant transformation of hepatocytes. At least four of the 10 HCV gene products, namely core, NS3, NS5A and NS5B play roles in several potentially oncogenic pathways. Induction of both endoplasmic reticulum (ER) stress and oxidative stress by HCV proteins may also contribute to hepatocyte growth promotion. The current review identifies important functions of the viral proteins connecting HCV infections and potential for development of HCC. However, most of the putative transforming potentials of the HCV proteins have been defined in artificial cellular systems, and need to be established relevant to infection and disease models. The new insight into the mechanisms for HCV mediated disease progression may offer novel therapeutic targets for one of the most devastating human malignancies in the world today. PMID:21994721

  10. Hepatitis B virus infection and intrahepatic cholangiocarcinoma

    PubMed Central

    Zhou, Hua-Bang; Hu, Jing-Yi; Hu, He-Ping

    2014-01-01

    Intrahepatic cholangiocarcinoma (ICC) is a devastating malignant tumor arising from the peripheral intrahepatic bile duct epithelium. The incidence and mortality of ICC is markedly increasing over the past two decades worldwide, though the cause for this rise in incidence is unclear, thus intensifying the search for alternative etiological agents and pathogenetic mechanisms. Hepatolithiasis, primary sclerosing cholangitis, parasitic infection (Opisthorchis viverrini or Clonorchis sinensis), fibropolycystic liver disease, and chemical carcinogen exposure are thought to be the risk factors for ICC. Nevertheless, the majority of ICC patients do not have any of these risk factors, and none of the established risk factors can explain the recent increasing trend of ICC. Therefore, identifying other risk factors may lead to the prevention and early detection of ICC. Chronic hepatitis B virus (HBV) infection is the predominant cause of hepatocellular carcinoma in HBV-endemic areas. This review discusses the evidence implicating chronic HBV infection as a likely etiology of ICC and the pathogenetic mechanisms that might be involved. PMID:24914333

  11. [Hepatitis E virus seroprevalence: a reappraisal].

    PubMed

    Covarrubías, Natalia; Hurtado, Carmen; Díaz, Alex; Mezzano, Gabriel; Brahm, Javier; Venegas, Mauricio

    2015-08-01

    Reported seroprevalence of hepatitis E virus (HEV) in developed countries is between 0.3-53%. Published data relies on the assays used and its technical performance. Sensitivity on new available tests has improved, which has changed HEV seroprevalence around the world. We re-evaluated retrospectively, 178 serum samples of patients with previous anti HEV IgG determination between 2009 and 2012. Initial analysis was performed with ELISA kit Genelabs (Singapore), with 7.3% positivity. The reevaluation was done with ELISA kit AccuDiag TM HEV-IgG (Diagnostic Automation, United States), with reported sensitivity and specificity over 99.8%. With the new assay, 32.6% positive samples were found, significantly greater to the previous result (p<0.001) (4.5 times more). There were no differences in gender but a significant association between age and HEV IgG seropositivity was found (p<0.001). This suggests that previous testing might have underestimated HEV seroprevalence in Chile, which should be reevaluated using the new available test. PMID:26436799

  12. Hepatitis C virus genotypes in Myanmar

    PubMed Central

    Win, Nan Nwe; Kanda, Tatsuo; Nakamoto, Shingo; Yokosuka, Osamu; Shirasawa, Hiroshi

    2016-01-01

    Myanmar is adjacent to India, Bangladesh, Thailand, Laos and China. In Myanmar, the prevalence of hepatitis C virus (HCV) infection is 2%, and HCV infection accounts for 25% of hepatocellular carcinoma. In this study, we reviewed the prevalence of HCV genotypes in Myanmar. HCV genotypes 1, 3 and 6 were observed in volunteer blood donors in and around the Myanmar city of Yangon. Although there are several reports of HCV genotype 6 and its variants in Myanmar, the distribution of the HCV genotypes has not been well documented in areas other than Yangon. Previous studies showed that treatment with peginterferon and a weight-based dose of ribavirin for 24 or 48 wk could lead to an 80%-100% sustained virological response (SVR) rates in Myanmar. Current interferon-free treatments could lead to higher SVR rates (90%-95%) in patients infected with almost all HCV genotypes other than HCV genotype 3. In an era of heavy reliance on direct-acting antivirals against HCV, there is an increasing need to measure HCV genotypes, and this need will also increase specifically in Myanmar. Current available information of HCV genotypes were mostly from Yangon and other countries than Myanmar. The prevalence of HCV genotypes in Myanmar should be determined. PMID:27468202

  13. Evaluation of avian influenza virus isolated from ducks as a potential live vaccine candidate against novel H7N9 viruses.

    PubMed

    Jiang, Wen-Ming; Wang, Su-Chun; Liu, Hua-Lei; Yu, Jian-Min; Du, Xiang; Hou, Guang-Yu; Li, Jin-Ping; Liu, Shuo; Wang, Kai-Cheng; Zhuang, Qing-Ye; Liu, Xiang-Ming; Chen, Ji-Ming

    2014-11-12

    Recent outbreaks of a novel H7N9 avian influenza virus in humans in China raise pandemic concerns and underscore an urgent need to develop effective vaccines. Theoretically, live influenza vaccines are of multiple advantages over traditional inactivated influenza vaccines to be used in a pandemic, because they can be produced rapidly, safely, and inexpensively. However, studies on live vaccines against the novel H7N9 virus are limited. In this study, we evaluated a potential live influenza vaccine candidate using an H7N3 avian influenza virus isolated from ducks with controls of two recombinant viruses generated through reverse genetics. The potential candidate could be produced efficiently using chicken embryonated eggs, and is homogenous to the novel H7N9 virus in their viral hemagglutinin genes. The potential candidate is likely low pathogenic to birds and mammals, and likely sensitive to oseltamivir and amantadine, as suggested by its genomic sequences. Its low pathogenicity was further supported through inoculation in mice, chicken embryonated eggs and chickens. Specific antibodies elicited in mice were detectable at least during the period between day 14 and day 56 after intranasal administration of the candidate for one time. Titers of the specific antibodies increased significantly with a boost intranasal administration or a higher inoculation dose. The induced specific antibodies were of substantial cross-reactivity with the novel H7N9 virus. These primary but promising evaluation data suggest that the duck influenza virus could be used as a potential live vaccine candidate, favorably through a prime-boost route, to mitigate the severity of the possible pandemic caused by the newly emerging H7N9 virus, and is valuable to be further evaluated. PMID:25285880

  14. Development and field application of a competitive enzyme-linked immunosorbent assay for detection of Newcastle disease virus antibodies in chickens and ducks.

    PubMed

    Phan, L V; Park, M-J; Kye, S-J; Kim, J-Y; Lee, H-S; Choi, K-S

    2013-08-01

    A competitive enzyme-linked immunosorbent assay (C-ELISA) using a baculovirus-expressed recombinant nucleocapsid protein antigen (rNDV-N) and an rNDV-N-specific monoclonal antibody (5B3) was developed for the detection of Newcastle disease virus (NDV) antibodies, and its diagnostic performance was evaluated. The specificity and sensitivity of the C-ELISA was found to be 98.4 and 98.9%, respectively, for chickens, and 98.2 and 97.9% for ducks. However, the C-ELISA showed weak cross-reaction with hyperimmune antisera to some other avian paramyxovirus serotypes. In all experimentally vaccinated chickens, seroconversion rates at 7 d postinoculation were 100 and 40% when measured by C-ELISA and hemagglutination inhibition (HI), respectively. In field trials, the C-ELISA showed positive results in 98.9% of HI-positive sera and 40.8% of HI-negative sera from NDV-vaccinated chickens (n = 705). In domestic ducks (n = 158) from NDV-positive duck farms (n = 8), the positive rates according to C-ELISA were significantly higher than those according to the HI test. At the same time, 98.1% of ducks (n = 209) from NDV-negative duck farms (n = 11) were also negative by C-ELISA. Our results indicate that C-ELISA could be a useful alternative to HI testing for detecting NDV antibodies in different avian species such as chickens and ducks. PMID:23873550

  15. Hepatitis B virus and hepatitis C virus infection in healthcare workers

    PubMed Central

    Coppola, Nicola; De Pascalis, Stefania; Onorato, Lorenzo; Calò, Federica; Sagnelli, Caterina; Sagnelli, Evangelista

    2016-01-01

    Approximately 3 million healthcare workers per year receive an injury with an occupational instrument, with around 2000000 exposures to hepatitis B virus (HBV) and 1000000 to hepatitis C virus (HCV). Although an effective HBV vaccine has been available since the early eighties, and despite the worldwide application of universal vaccination programs started in the early nineties, HBV still remains a prominent agent of morbidity and mortality. There is no vaccine to limit the diffusion of HCV infection, which progresses to chronicity in the majority of cases and is a major cause of morbidity and mortality worldwide due to a chronic liver disease. Healthcare workers are frequently exposed by a mucosal-cutaneous or percutaneous route to accidental contact with human blood and other potentially infectious biological materials while carrying out their occupational duties. Mucosal-cutaneous exposure occurs when the biological material of a potentially infected patient accidentally comes in contact with the mucous membranes of the eyes or mouth or with the skin of a healthcare worker. Percutaneous exposure occurs when an operator accidentally injures himself with a sharp contaminated object, like a needle, blade or other sharp medical instrument. About 75% of the total occupational exposure is percutaneous and 25% mucosal-cutaneous, the risk of infecting a healthcare worker being higher in percutaneous than in mucosal-cutaneous exposure. All healthcare workers should be considered for HBV vaccination and should meticulously apply the universal prophylactic measures to prevent exposure to HBV and HCV. PMID:26925201

  16. Distribution of Hepatitis C Virus Genotypes Among Patients With Hepatitis C Virus Infection in Hormozgan, Iran

    PubMed Central

    Mousavi, Seyedeh Farzaneh; Moosavy, Seyed Hamid; Alavian, Seyed Moayed; Eghbali, Hajar; Mahboobi, Hamidreza

    2013-01-01

    Background More than 170 million people in the world are infected with Hepatitis C virus (HCV). Determination of HCV genotype before starting the treatment is required, because HCV genotype affects the course of treatment and drug dosage Objectives We aimed to evaluate HCV genotypes among patients with positive results for anti-HCV in Bandar Abbas from 2011 to 2012. Patients and Methods Five hundred and nine consecutive patients with established chronic HCV infection referred to Behavioral Diseases Consultation Center, Blood Transfusion and Center for Special Diseases from March 2011 to March 2012 were enrolled in this cross sectional study. Five mL of peripheral blood was taken from precipitants and viral RNA extracted after plasma separation. Hepatitis C virus RNA was detected by reverse transcriptase-nested polymerase chain reaction (RT-nested PCR) assay and then HCV genotypes analyzed using restriction fragment length polymorphism (RFLP) method. Results In overall, 509 patients enrolled to this study. The mean age of these patients was 38.87 ± 9.55 years ranging from 1 to 90 years. Routs of transmission were: 238 (46.7%) inject of substance, 149 (29.3%) unknown rout, 62 (12.2%) blood transfusion, 50 (9.8%) sexual contact, and 10 (2%) mother to child. Frequency of HCV genotypes were: 316 (62.1%) 1a, 117 (23%) 1b, and 76 (14.9%) 3a. there was no significant association between HCV genotypes and gender, educational degree, risk factor of Hepatitis C, job, monthly income, HIV infection, Hepatitis B virus (HBV) infection, Intravenous drug injection, and underlying disease (P > 0.05). Conclusions This results the same as many similar studies demonstrated that common HCV genotypes in Iranian patients were 1a, 3a and 1b, respectively. Patients with 1a and 1b genotypes have lower responses to interferon treatment, and it is reasonable to perform early screening to diagnose and determine HCV genotype for effective treatment and diagnose high-risk cases. PMID:24403914

  17. Hepatitis A Virus and Hepatitis E Virus Seroprevalence Among Blood Donors in Tehran, Iran

    PubMed Central

    Hesamizadeh, Khashayar; Sharafi, Heidar; Keyvani, Hossein; Alavian, Seyed Moayed; Najafi-Tireh Shabankareh, Azar; Sharifi Olyaie, Roghiyeh; Keshvari, Maryam

    2016-01-01

    Background Hepatitis A virus (HAV) and Hepatitis E virus (HEV) are both transmitted by the fecal-oral route and are known as the leading causes of acute viral hepatitis in the world, especially in developing countries. There is a lack of updated data on HAV and HEV seroprevalence in Iran. Objectives The aim of this study was to determine the seroprevalence of HAV and HEV among a group of blood donors in Tehran, Iran. Materials and Methods A cross-sectional study was performed from July 2014 to December 2014, on a total of 559 blood donors referred to the Tehran blood transfusion center. The serum samples were tested for antibodies to HAV and HEV, using the enzyme-linked immunosorbent assay. Results In the present study, 536 (95.9%) cases were male and 23 (4.1%) female with mean age of 38 years. Out of 559 blood donors, 107 (19.1%) were first-time donors, 163 (29.2%) lapsed donors and 289 (51.7%) regular donors. Anti-HAV was found in 395 (70.7%) and anti-HEV in 45 (8.1%) of the blood donors. The HAV and HEV seroprevalence increased by age. There was no significant difference between genders in terms of anti-HAV and anti-HEV status. The HAV and HEV seroprevalence was significantly related to the level of education, where the donors with higher level of education had lower rate of HAV and HEV seroprevalence. The HAV and HEV seroprevalence was significantly higher in regular and lapsed donors than in first-time donors. Conclusions The present study showed that both HAV and HEV infections are still endemic in Iran. PMID:27110256

  18. Homo- and Heterosubtypic Low Pathogenic Avian Influenza Exposure on H5N1 Highly Pathogenic Avian Influenza Virus Infection in Wood Ducks (Aix sponsa)

    PubMed Central

    Costa, Taiana P.; Brown, Justin D.; Howerth, Elizabeth W.; Stallknecht, David E.; Swayne, David E.

    2011-01-01

    Wild birds in the Orders Anseriformes and Charadriiformes are the natural reservoirs for avian influenza (AI) viruses. Although they are often infected with multiple AI viruses, the significance and extent of acquired immunity in these populations is not understood. Pre-existing immunity to AI virus has been shown to modulate the outcome of a highly pathogenic avian influenza (HPAI) virus infection in multiple domestic avian species, but few studies have addressed this effect in wild birds. In this study, the effect of pre-exposure to homosubtypic (homologous hemagglutinin) and heterosubtypic (heterologous hemagglutinin) low pathogenic avian influenza (LPAI) viruses on the outcome of a H5N1 HPAI virus infection in wood ducks (Aix sponsa) was evaluated. Pre-exposure of wood ducks to different LPAI viruses did not prevent infection with H5N1 HPAI virus, but did increase survival associated with H5N1 HPAI virus infection. The magnitude of this effect on the outcome of the H5N1 HPAI virus infection varied between different LPAI viruses, and was associated both with efficiency of LPAI viral replication in wood ducks and the development of a detectable humoral immune response. These observations suggest that in naturally occurring outbreaks of H5N1 HPAI, birds with pre-existing immunity to homologous hemagglutinin or neuraminidase subtypes of AI virus may either survive H5N1 HPAI virus infection or live longer than naïve birds and, consequently, could pose a greater risk for contributing to viral transmission and dissemination. The mechanisms responsible for this protection and/or the duration of this immunity remain unknown. The results of this study are important for surveillance efforts and help clarify epidemiological data from outbreaks of H5N1 HPAI virus in wild bird populations. PMID:21253608

  19. Hepatic enzyme activity after combined administration of methylmercury, lead and cadmium in the pekin duck

    SciTech Connect

    Jordan, S.A.; Bhatnagar, M.K. )

    1990-04-01

    In order to assess adequately the environmental impact of heavy metals it is important to consider that they may occur simultaneously in the environment, where they may interact to alter their individual toxicities on living systems. Metals such as mercury (Hg), lead (Pb) and cadmium (Cd) can be found in all levels of the polluted ecosystem, and in animals inhabiting such areas. In the polluted aquatic environment waterfowl have been noted to accumulate high levels of these metals in their tissues. A major toxic manifestation of heavy metal exposure is the perturbation of a wide range of enzyme systems in virtually all subcellular compartments. With the exception of lead, little data is available on the effects of metals on avian enzyme systems. The present report describes the effects observed in vivo on acid phosphatase (AP), glutathione S-transferase (GST) and cytochrome c oxidase (cyt c ox) in the liver of pekin ducks exposed to combinations of methylmercury (MeHg), lead and cadmium.

  20. Establishing a TaqMan-Based Real-Time PCR Assay for the rapid detection and quantification of the newly emerged duck tembusu virus

    PubMed Central

    2011-01-01

    To establish an accurate, rapid, and a quantifiable method for the detection of the newly emerged duck Tembusu virus (DTMUV) that recently caused a widespread infectious disease in ducks in China, we developed a TaqMan-based real-time PCR assay by using E gene-specific primers and a TaqMan probe. This real-time PCR assay was 100 times more sensitive than the conventional PCR. The reproducibility and specificity of the real-time PCR assay were confirmed using plasmids containing E genes or RNAs and DNAs extracted from well-known viruses causing duck diseases. The reliability of this real-time PCR assay was confirmed in 19 of the 24 swab samples, 22 of the 24 tissue samples collected from experimentally infected ducks, as well as 15 of the 21 clinical samples collected from sick ducks since they were verified as DTMUV-positive. The results reveal that the newly established real-time PCR assay might be a useful diagnostic method for epidemiologically investigating and closely observing the newly emerged DTMUV. PMID:21978536

  1. Development of RT-LAMP and real-time RT-PCR assays for the rapid detection of the new duck Tembusu-like BYD virus.

    PubMed

    Jiang, Tao; Liu, Juan; Deng, Yong-Qiang; Su, Jing-Liang; Xu, Li-Juan; Liu, Zhi-Hui; Li, Xiao-Feng; Yu, Xue-Dong; Zhu, Shun-Ya; Gao, George Fu; Qin, E-De; Qin, Cheng-Feng

    2012-12-01

    A new duck Tembusu virus (TMUV), also known as BYD virus, has been identified as the causative agent for the emerging duck egg-drop syndrome in mainland China. The rapid spread and wide distribution of the new TMUV in mainland China result in heavy loss to the poultry industry and pose great threats to public health. Rapid and sensitive detection methods are critical for prevention and control of TMUV infections. In this study, a reverse-transcription loop-mediated isothermal amplification assay (RT-LAMP) and an SYBR Green-I-based real-time RT-PCR assay specific for the duck TMUV were developed and validated with laboratory and field samples, respectively. The detection limits were 1 × 10(-4) and 1 × 10(-3) PFU per reaction for the RT-LAMP assay and real-time RT-PCR assay, respectively. The specificities were analyzed with other related members of the genus Flavivirus, and no cross-reaction was observed. Furthermore, both assays were evaluated with field samples, and they exhibited high sensitivity and specificity. In addition, the real-time RT-PCR assay worked well in viral load analysis, which revealed that the spleen may be the primary target for the replication of new duck TMUV in ducks. The TMUV-specific RT-LAMP and real-time RT-PCR assays will provide useful tools for the diagnosis and epidemiological surveillance of TMUV infection. PMID:22865206

  2. Hepatitis B Virus X and Regulation of Viral Gene Expression.

    PubMed

    Slagle, Betty L; Bouchard, Michael J

    2016-03-01

    The efficient replication of hepatitis B virus (HBV) requires the HBV regulatory hepatitis B virus X (HBx) protein. The exact contributions of HBx are not fully understood, in part because of the limitations of the assays used for its study. When HBV replication is driven from a plasmid DNA, the contribution of HBx is modest. However, there is an absolute requirement for HBx in assays that recapitulate the infectious virus life cycle. There is much evidence that HBx can contribute directly to HBV replication by acting on viral promoters embedded within protein coding sequences. In addition, HBx may also contribute indirectly by modulating cellular pathways to benefit virus replication. Understanding the mechanism(s) of HBx action during virus replication may provide insight into novel ways to disrupt chronic HBV replication. PMID:26747833

  3. Unfolded protein response in hepatitis C virus infection

    PubMed Central

    Chan, Shiu-Wan

    2014-01-01

    Hepatitis C virus (HCV) is a single-stranded, positive-sense RNA virus of clinical importance. The virus establishes a chronic infection and can progress from chronic hepatitis, steatosis to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The mechanisms of viral persistence and pathogenesis are poorly understood. Recently the unfolded protein response (UPR), a cellular homeostatic response to endoplasmic reticulum (ER) stress, has emerged to be a major contributing factor in many human diseases. It is also evident that viruses interact with the host UPR in many different ways and the outcome could be pro-viral, anti-viral or pathogenic, depending on the particular type of infection. Here we present evidence for the elicitation of chronic ER stress in HCV infection. We analyze the UPR signaling pathways involved in HCV infection, the various levels of UPR regulation by different viral proteins and finally, we propose several mechanisms by which the virus provokes the UPR. PMID:24904547

  4. Sampling of sea ducks for influenza A viruses in Alaska during winter provides lack of evidence for epidemiological peak of infection.

    USGS Publications Warehouse

    Ramey, Andy M.; Reeves, Andrew B.; Poulson, Rebecca L.; Wasley, Jeff; Esler, Daniel N.; Stalknecht, David E.

    2015-01-01

    Sampling of sea ducks for influenza A viruses in Alaska during winter provided no evidence for an epidemiologic peak of infection. Isolates were recovered, however, that provide information on viral diversity and dispersal that may not be realized through sampling efforts focused on other avian taxa.

  5. [HIV infection and parenteral virus hepatitis in the Krasnodar territory].

    PubMed

    Larin, F I; Lebedev, V V; Red'ko, A N

    2005-01-01

    The analysis of the morbidity dynamics of HIV infection, hepatitis B and C in the Krasnodar territory for 1996-2003 is presented. The tendency of strengthening direct correlation between age-dependent rates in these groups of diseases has been established. The correlation coefficient (rxy) is at present +0.851 (HIV infection-virus hepatitis B) and +0.892 (HIV infection-virus hepatitis C). The highest levels of primary morbidity are registered in persons aged 20-39 years. The established epidemiological parallels between HIV infection and parenteral hepatitis require the development of the unified strategy of the prophylaxis of these diseases on the federal and regional levels. PMID:16028521

  6. Glucose abnormalities in hepatitis C virus infection.

    PubMed

    Huang, Jee-Fu; Yu, Ming-Lung; Dai, Chia-Yen; Chuang, Wan-Long

    2013-02-01

    Hepatitis C virus (HCV) infection is one of the most important causes of cirrhosis and hepatocellular carcinoma and has a tremendous impact on public health worldwide. HCV is both hepatotropic and lymphotropic. Replication of HCV in diseased extrahepatic organs and tissues may either trigger latent autoimmunity or induce autoimmune disorders. In addition to established liver injury, type 2 diabetes mellitus (T2DM) is an important feature of extrahepatic metabolic disorders which is attributed to HCV infection. It also has some impact on the disease activity, disease course, clinical outcomes, and treatment efficacy of antiviral therapy. Previous experimental and clinical findings have highly suggested that HCV per se is diabetogenic. The cause-effect interaction between a common endocrine disorder and an infectious disease is an important issue to elucidate. Although the precise mechanisms whereby HCV infection leads to insulin resistance (IR) and glucose abnormalities are not entirely clear, it differs from the usual pathogenesis of T2DM in those with non-HCV liver diseases. This review initially highlights epidemiological and pathophysiological studies addressing the mutual link between chronic HCV infection (CHC) and T2DM. The characteristics of glucose abnormalities in this special population are depicted from the current evidence. The mutual roles of IR and CHC with respect to the prediction of treatment efficacy, how treatment response affects IR, and the role of pancreatic beta cell function in the entire suite are discussed. With the rapid progression of antiviral therapy for CHC in the past decade, we have also listed some points of future perspective in this issue. PMID:23347806

  7. 21 CFR 610.47 - Hepatitis C virus (HCV) “lookback” requirements.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Hepatitis C virus (HCV) âlookbackâ requirements... Disease Agents § 610.47 Hepatitis C virus (HCV) “lookback” requirements. (a) If you are an establishment... after a donor tests reactive for evidence of hepatitis C virus (HCV) infection when tested under §...

  8. 21 CFR 610.47 - Hepatitis C virus (HCV) “lookback” requirements.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Hepatitis C virus (HCV) âlookbackâ requirements... Disease Agents § 610.47 Hepatitis C virus (HCV) “lookback” requirements. (a) If you are an establishment... after a donor tests reactive for evidence of hepatitis C virus (HCV) infection when tested under §...

  9. 21 CFR 610.47 - Hepatitis C virus (HCV) “lookback” requirements.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Hepatitis C virus (HCV) âlookbackâ requirements... Disease Agents § 610.47 Hepatitis C virus (HCV) “lookback” requirements. (a) If you are an establishment... after a donor tests reactive for evidence of hepatitis C virus (HCV) infection when tested under §...

  10. 21 CFR 610.47 - Hepatitis C virus (HCV) “lookback” requirements.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Hepatitis C virus (HCV) âlookbackâ requirements... Disease Agents § 610.47 Hepatitis C virus (HCV) “lookback” requirements. (a) If you are an establishment... after a donor tests reactive for evidence of hepatitis C virus (HCV) infection when tested under §...

  11. 21 CFR 610.47 - Hepatitis C virus (HCV) “lookback” requirements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Hepatitis C virus (HCV) âlookbackâ requirements... Disease Agents § 610.47 Hepatitis C virus (HCV) “lookback” requirements. (a) If you are an establishment... after a donor tests reactive for evidence of hepatitis C virus (HCV) infection when tested under §...

  12. Hepatitis E Virus Infection among Solid Organ Transplant Recipients, the Netherlands

    PubMed Central

    Pas, Suzan D.; de Man, Rob A.; Mulders, Claudia; Balk, Aggie H.M.M.; van Hal, Peter T.W.; Weimar, Willem; Koopmans, Marion P.G.; Osterhaus, Albert D.M.E.

    2012-01-01

    We screened 1,200 living heart, lung, liver, and kidney transplant recipients for hepatitis E virus infection by reverse transcription PCR. In 12 (1%) patients, hepatitis E virus infection was identified; in 11 patients, chronic infection developed. This immunocompromised population is at risk for hepatitis E virus infection. PMID:22516170

  13. Virus and Host Testing to Manage Chronic Hepatitis B.

    PubMed

    Wong, Grace Lai-Hung; Wong, Vincent Wai-Sun; Chan, Henry Lik-Yuen

    2016-06-01

    Chronic hepatitis B virus (HBV) infection is a major cause of cirrhosis and hepatocellular carcinoma worldwide. The past 50 years have seen rapid developments in HBV testing. Beginning from traditional serologic tests, the availability of sensitive HBV DNA assays allows a thorough understanding of the virology and natural history of chronic HBV infection. Quantification of hepatitis B surface antigen levels reflects the amount and transcriptional activities of covalently closed circular DNA in the liver and may be used to evaluate the stage of disease and guide antiviral therapy. The natural history of chronic HBV infection is also a manifestation of the interaction between the host and the virus, and recent genomic works have shed light on the host-virus relationship and may provide novel tests in the future. This review highlights recent advances in the application of HBV tests in the management of chronic hepatitis B. PMID:27190319

  14. Experimental infection of highly and low pathogenic avian influenza viruses to chickens, ducks, tree sparrows, jungle crows, and black rats for the evaluation of their roles in virus transmission.

    PubMed

    Hiono, Takahiro; Okamatsu, Masatoshi; Yamamoto, Naoki; Ogasawara, Kohei; Endo, Mayumi; Kuribayashi, Saya; Shichinohe, Shintaro; Motohashi, Yurie; Chu, Duc-Huy; Suzuki, Mizuho; Ichikawa, Takaya; Nishi, Tatsuya; Abe, Yuri; Matsuno, Keita; Tanaka, Kazuyuki; Tanigawa, Tsutomu; Kida, Hiroshi; Sakoda, Yoshihiro

    2016-01-15

    Highly pathogenic avian influenza viruses (HPAIVs) have spread in both poultry and wild birds. Determining transmission routes of these viruses during an outbreak is essential for the control of avian influenza. It has been widely postulated that migratory ducks play crucial roles in the widespread dissemination of HPAIVs in poultry by carrying viruses along with their migrations; however close contacts between wild migratory ducks and poultry are less likely in modern industrial poultry farming settings. Therefore, we conducted experimental infections of HPAIVs and low pathogenic avian influenza viruses (LPAIVs) to chickens, domestic ducks, tree sparrows, jungle crows, and black rats to evaluate their roles in virus transmission. The results showed that chickens, ducks, sparrows, and crows were highly susceptible to HPAIV infection. Significant titers of virus were recovered from the sparrows and crows infected with HPAIVs, which suggests that they potentially play roles of transmission of HPAIVs to poultry. In contrast, the growth of LPAIVs was limited in each of the animals tested compared with that of HPAIVs. The present results indicate that these common synanthropes play some roles in influenza virus transmission from wild birds to poultry. PMID:26711036

  15. Yeast-recombinant hepatitis B vaccine: efficacy with hepatitis B immune globulin in prevention of perinatal hepatitis B virus transmission

    SciTech Connect

    Stevens, C.E.; Taylor, P.E.; Tong, M.J.; Toy, P.T.; Vyas, G.N.; Nair, P.V.; Weissman, J.Y.; Krugman, S.

    1987-05-15

    A yeast-recombinant hepatitis B vaccine was licensed recently by the Food and Drug administration and is now available. To assess the efficacy of the yeast-recombinant vaccine, the authors administered the vaccine in combination with hepatitis B immune globulin to high-risk newborns. If infants whose mothers were positive for both hepatitis B surface antigen and the e antigen receive no immunoprophylaxis, 70% to 90% become infected with the virus, and almost all become chronic carriers. Among infants in this study who received hepatitis B immune globulin at birth and three 5-/sup +/g doses of yeast-recombinant hepatitis B vaccine, only 4.8% became chronic carriers, a better than 90% level of protection and a rate that is comparable with that seen with immune globulin and plasma-derived hepatitis B vaccine. Hepatitis surface antigen and antibodies were detected by radioimmunoassay. These data suggest that, in this high-risk setting, the yeast-recombinant vaccine is as effective as the plasma-derived vaccine in preventing hepatitis B virus infection and the chronic carrier state.

  16. Vaccination of chimpanzees against infection by the hepatitis C virus.

    PubMed Central

    Choo, Q L; Kuo, G; Ralston, R; Weiner, A; Chien, D; Van Nest, G; Han, J; Berger, K; Thudium, K; Kuo, C

    1994-01-01

    A high incidence of community-acquired hepatitis C virus infection that can lead to the progressive development of chronic active hepatitis, liver cirrhosis, and primary hepatocellular carcinoma occurs throughout the world. A vaccine to control the spread of this agent that represents a major cause of chronic liver disease is therefore needed. Seven chimpanzees (Pan troglodytes) have been immunized with both putative envelope glycoproteins [E1 (gp33) and E2 (gp72)] that were copurified from HeLa cells infected with a recombinant vaccinia virus expression vector. Despite the induction of a weak humoral immune response to these viral glycoproteins in experimentally infected chimpanzees, a strong humoral immune response was obtained in all vaccines. The five highest responders showed complete protection against an i.v. challenge with homologous hepatitis C virus 1. The remaining two vaccines became infected, but both infection and disease may have been ameliorated in comparison with four similarly challenged control chimpanzees, all of which developed acute hepatitis and chronic infections. These results provide considerable encouragement for the eventual control of hepatitis C virus infection by vaccination. PMID:7509068

  17. Vaccination of chimpanzees against infection by the hepatitis C virus.

    PubMed

    Choo, Q L; Kuo, G; Ralston, R; Weiner, A; Chien, D; Van Nest, G; Han, J; Berger, K; Thudium, K; Kuo, C

    1994-02-15

    A high incidence of community-acquired hepatitis C virus infection that can lead to the progressive development of chronic active hepatitis, liver cirrhosis, and primary hepatocellular carcinoma occurs throughout the world. A vaccine to control the spread of this agent that represents a major cause of chronic liver disease is therefore needed. Seven chimpanzees (Pan troglodytes) have been immunized with both putative envelope glycoproteins [E1 (gp33) and E2 (gp72)] that were copurified from HeLa cells infected with a recombinant vaccinia virus expression vector. Despite the induction of a weak humoral immune response to these viral glycoproteins in experimentally infected chimpanzees, a strong humoral immune response was obtained in all vaccines. The five highest responders showed complete protection against an i.v. challenge with homologous hepatitis C virus 1. The remaining two vaccines became infected, but both infection and disease may have been ameliorated in comparison with four similarly challenged control chimpanzees, all of which developed acute hepatitis and chronic infections. These results provide considerable encouragement for the eventual control of hepatitis C virus infection by vaccination. PMID:7509068

  18. Isolation and molecular characterization of reassortant H11N3 subtype avian influenza viruses isolated from domestic ducks in Zhejiang Province in China.

    PubMed

    Wu, Haibo; Peng, Xiuming; Peng, Xiaorong; Wu, Nanping

    2016-10-01

    In July 2013, six H11N3 subtype avian influenza viruses (AIVs) were isolated from domestic ducks in Zhejiang Province in Eastern China. These strains were characterized by whole genome sequencing with subsequent phylogenetic analysis and genetic comparison. Phylogenetic analysis of all eight viral genes showed that these strains clustered in the AIV Eurasian lineage, and these strains received their genes from H11, H7, and H1 AIVs in Eastern China. These strains were found to be minimally pathogenic in mice, and were able to replicate in mice without prior adaptation. Continued surveillance is needed considering the important role of domestic ducks in AIV reassortment. PMID:27142079

  19. Detection of Specific Antibodies against Tembusu Virus in Ducks by Use of an E Protein-Based Enzyme-Linked Immunosorbent Assay

    PubMed Central

    Yin, Xiuchen; Lv, Rang; Chen, Xiaodan; Hua, Ronghong

    2013-01-01

    We developed an enzyme-linked immunosorbent assay (ELISA) using eukaryotically expressed E protein as the antigen (termed E-ELISA) to detect antibodies to tembusu virus (TMUV) in ducks. The E-ELISA did not react with antisera to other known pathogens, indicating the E protein is specific for recognizing anti-TMUV antibodies. Compared to the serum neutralization test, the specificity and sensitivity of the E-ELISA was 93.2 and 97.8%, respectively. Therefore, this E-ELISA is a sensitive and rapid method for detecting antibodies against TMUV in ducks. PMID:23616462

  20. Taraxacum mongolicum extract exhibits a protective effect on hepatocytes and an antiviral effect against hepatitis B virus in animal and human cells.

    PubMed

    Jia, Yuan-Yuan; Guan, Rong-Fa; Wu, Yi-Hang; Yu, Xiao-Ping; Lin, Wen-Yan; Zhang, Yong-Yong; Liu, Tao; Zhao, Jun; Shi, Shu-Yun; Zhao, Yu

    2014-04-01

    In order to validate the antiviral effect against hepatitis B virus (HBV) of Taraxacum mongolicum (T. mongolicum), the protective effect on hepatocytes, and antiviral properties against duck hepatitis B virus (DHBV) and HBV of T. mongolicum extract (TME) were evaluated in chemically-injured neonatal rat hepatocytes, DHBV-infected duck fetal hepatocytes and HBV-transfected HepG2.2.15 cells, respectively. The results demonstrated that TME at 50-100 µg/ml improved D-galactosamine (D-GalN), thioacetamide (TAA) and tert-butyl hydroperoxide (t-BHP)-injured rat hepatocytes, and produced protection rates of 42.2, 34.6 and 43.8% at 100 µg/ml, respectively. Furthermore, TME at 1-100 µg/ml markedly inhibited DHBV DNA replication. Additionally, TME at 25-100 µg/ml reduced HBsAg and HBeAg levels and produced inhibition rates of 91.39 and 91.72% at 100 µg/ml, respectively. TME markedly inhibited HBV DNA replication at 25-100 µg/ml. The results demonstrate the potent antiviral effect of T. mongolicum against HBV effect. The protective of TME effect on hepatocytes may be achieved by its ability to ameliorate oxidative stress. The antiviral properties of TME may contribute to blocking protein synthesis steps and DNA replication. Furthermore, major components of TME were quantificationally analyzed. These data provide scientific evidence supporting the traditional use of TME in the treatment of hepatitis. PMID:24481875

  1. Variability and pathogenicity of hepatitis E virus genotype 3 variants

    PubMed Central

    Ijaz, Samreen; Tedder, Richard S.; Hogema, Boris; Zaaijer, Hans L.; Izopet, Jacques; Bradley-Stewart, Amanda; Gunson, Rory; Harvala, Heli; Kokki, Inka; Simmonds, Peter

    2015-01-01

    Infection with hepatitis E virus (HEV) can be clinically inapparent or produce symptoms and signs of hepatitis of varying severity and occasional fatality. This variability in clinical outcomes may reflect differences in host susceptibility or the presence of virally encoded determinants of pathogenicity. Analysis of complete genome sequences supports the division of HEV genotype 3 (HEV-3) variants into three major clades: 3ra comprising HEV isolates from rabbits, and 3efg and 3abchij comprising the corresponding named subtypes derived from humans and pigs. Using this framework, we investigated associations between viral genetic variability of HEV-3 in symptomatic and asymptomatic infections by comparing HEV-3 subgenomic sequences previously obtained from blood donors with those from patients presenting with hepatitis in the UK (54 blood donors, 148 hepatitis patients), the Netherlands (38 blood donors, 119 hepatitis patients), France (24 blood donors, 55 hepatitis patients) and Germany (14 blood donors, 36 hepatitis patients). In none of these countries was evidence found for a significant association between virus variants and patient group (P>0.05 Fisher's exact test). Furthermore, within a group of 123 patients in Scotland with clinically apparent HEV infections, we found no evidence for an association between variants of HEV-3 and disease severity or alanine aminotransferase level. The lack of detectable virally encoded determinants of disease outcomes in HEV-3 infection implies a more important role for host factors in its clinical phenotype. PMID:26282123

  2. Role of hepatitis C virus in chronic liver disease occurring after orthotopic liver transplantation.

    PubMed Central

    Pastore, M; Willems, M; Cornu, C; Buts, J P; Reding, R; de Ville de Goyet, J; Rahier, J; Otte, J B; Yap, S H; Sokal, E M

    1995-01-01

    Paediatric orthotopic liver transplant recipients may develop chronic hepatitis after surgery. To investigate the role of hepatitis C virus in this pathology a cohort of 249 paediatric orthotopic liver transplant recipients was studied. Sixteen children (6.4%) were found to have chronic hepatitis C virus hepatitis after orthotopic liver transplantation. All but one of them had serum transaminase values which were persistently raised two to eight times the upper limit of normal. Thirteen were positive for both serology and serum hepatitis C virus RNA. Serum hepatitis C virus RNA detection occurred five to 33 months before hepatitis C virus antibodies. Liver tissue hepatitis C virus RNA and hepatitis C virus core antigen were detected in five. In one patient, tissue hepatitis C virus core antigen was detected when other tests for hepatitis C were negative. Two patients had positive human cytomegalovirus serum antibodies and RNA before transplantation. Although serum hepatitis C virus RNA was not detected after transplantation, serum enzyme immunosorbent assay and tissue core antigen were still detectable in both patients. In another child, serum hepatitis C virus RNA was positive and hepatitis C virus core antigen was found on a liver biopsy specimen but antihepatitis C virus antibodies were negative as well as liver hepatitis C virus RNA. No patient developed severe liver disease or cirrhosis during a follow up of up to 72 months. It is concluded that hepatitis C virus is a significant cause of morbidity after paediatric orthotopic liver transplantation. Diagnosis cannot rely on serological testing only. The patients remained stable on follow up, but longer prospective histological studies remain necessary to establish prognosis. PMID:7618905

  3. [MOLECULAR BIOLOGY OF HEPATITIS B VIRUS AND IMMUNOPATHOGENESIS OF CHRONIC VIRAL HEPATITIS B].

    PubMed

    Balmasova, I P; Sepiashvili, R I; Malova, E S

    2016-01-01

    Chronic hepatitis B belongs to a category of socially significant diseases due to its wide abundance in the world and high frequency of unfavourable outcomes of this disease. Features of interaction of hepatitis B virus with human immune system, accompanying development of mechanisms of escape from immunological control, is the basis of development of chronic hepatitis B. Molecular-biological features of hepatitis B virus are the basis of the indicated mechanisms, and the content of this review is their examination. Herewith, stages of immunopathogenesis of this disease is the basis of characteristics of interaction of viral proteins with cells of immune system, and isolation of those is accepted in contemporary foreign literature. PMID:27228681

  4. Genotype characterization of occult hepatitis B virus strains among Egyptian chronic hepatitis C patients.

    PubMed

    Kishk, R; Atta, H Aboul; Ragheb, M; Kamel, M; Metwally, L; Nemr, N

    2014-02-01

    Chronic hepatitis C virus (HCV) infection combined with occult hepatitis B virus (HBV) infection has been associated with increased risk of hepatitis, cirrhosis and hepatocellular carcinoma. This study aimed to determine the prevalence of occult HBV infection among Egyptian chronic HCV patients, the genotype and occurrence of surface gene mutations of HBV and the impact of co-infection on early response to treatment. The study enrolled 162 chronic HCV patients from Ismailia Fever Hospital, Egypt, who were HBV surface antigen-negative. All patients were given clinical assessment and biochemical, histological and virological examinations. HBV-DNA was detectable in sera from 3 patients out of the 40 patients who were positive for hepatitis B core antibody. These 3 patients were responsive to combination therapy at treatment week 12; only 1 of them had discontinued therapy by week 24. HBV genotype D was the only detectable genotype in those patients, with absence of "a" determinant mutations among those isolates. PMID:24945562

  5. The effect of age on the pathogenesis of a highly pathogenic avian influenza (HPAI) H5N1 virus in Pekin ducks (Anas platyrhynchos) infected experimentally

    PubMed Central

    Löndt, Brandon Z.; Núñez, Alejandro.; Banks, Jill; Alexander, Dennis J.; Russell, Christine; Richard‐ Löndt, Angela C.; Brown, Ian H.

    2009-01-01

    Background  Highly pathogenic avian influenza (HPAI) H5N1 viruses have recently displayed increased virulence for wild waterfowl. Objectives  To study the effect of host age on the shedding and tissue dissemination of a HPAI H5N1 virus in infected Pekin ducks. Methods  Pekin ducks in two age‐matched groups (n = 18), 8 and 12 weeks old (wo) were each infected with 106 EID50/0·1 ml of HPAI A/turkey/Turkey/1/05 (H5N1, clade 2·2). Each day for 5 days, birds were monitored clinically, and cloacal and oropharyngeal swabs collected, before three birds from each group were selected randomly for post‐mortem examination. Tissue samples were collected for examination by real‐time RT‐PCR, histopathology and immunohistochemistry (IHC). Results  Severe clinical signs, including incoordination and torticollis were observed in the 8 wo group resulting in 100% mortality by 4 dpi. Mild clinical signs were observed in the 12 wo group with no mortality. Real‐time RT‐PCR and IHC results demonstrated the systemic spread of H5N1 virus in birds of both age groups. Higher levels of virus shedding were detected in oropharyngeal swabs than in cloacal swabs, with similar levels of shedding detected in both age groups. Variations in level and temporal dissemination of virus within tissues of older ducks, and the presence of the virus in brain and heart were observed, which coincided with the appearance of clinical signs preceding death in younger birds. Conclusions  These results are consistent with reports of natural infections of wild waterfowl and poultry possibly indicating an age‐related association with dissemination and clinical outcome in ducks following infection with H5N1 HPAI virus. PMID:20021503

  6. Highly Pathogenic Avian Influenza Virus A/H5N1 Infection in Vaccinated Meat Duck Flocks in the Mekong Delta of Vietnam.

    PubMed

    Cuong, N V; Truc, V N T; Nhung, N T; Thanh, T T; Chieu, T T B; Hieu, T Q; Men, N T; Mai, H H; Chi, H T; Boni, M F; van Doorn, H R; Thwaites, G E; Carrique-Mas, J J; Hoa, N T

    2016-04-01

    We investigated episodes of suspected highly pathogenic avian influenza (HPAI)-like illness among 12 meat duck flocks in two districts in Tien Giang province (Mekong Delta, Vietnam) in November 2013. In total, duck samples from 8 of 12 farms tested positive for HPAI virus subtype A/haemagglutinin 5 and neuraminidase 1 (H5N1) by real-time RT-PCR. Sequencing results confirmed clade of 2.3.2.1.c as the cause of the outbreaks. Most (7/8) laboratory-confirmed positive flocks had been vaccinated with inactivated HPAI H5N1 clade 2.3.4 vaccines <6 days prior to onset of clinical signs. A review of vaccination data in relation to estimated production in the area suggested that vaccination efforts were biased towards larger flocks and that vaccination coverage was low [21.2% ducks vaccinated with two shots (range by district 7.4-34.9%)]. The low-coverage data, the experimental evidence of lack of cross-protection conferred by the currently used vaccines based on clade 2.3.4 together with the short lifespan of meat duck flocks (60-70 days), suggest that vaccination is not likely to be effective as a tool for control of H5N1 infection in meat duck flocks in the area. PMID:26748550

  7. Hepatitis C virus comes for dinner: How the hepatitis C virus interferes with autophagy

    PubMed Central

    Ploen, Daniela; Hildt, Eberhard

    2015-01-01

    Autophagy is a highly-regulated, conserved cellular process for the degradation of intracellular components in lysosomes to maintain the energetic balance of the cell. It is a pro-survival mechanism that plays an important role during development, differentiation, apoptosis, ageing and innate and adaptive immune response. Besides, autophagy has been described to be involved in the development of various human diseases, e.g., chronic liver diseases and the development of hepatocellular carcinoma. The hepatitis C virus (HCV) is a major cause of chronic liver diseases. It has recently been described that HCV, like other RNA viruses, hijacks the autophagic machinery to improve its replication. However, the mechanisms underlying its activation are conflicting. HCV replication and assembly occurs at the so-called membranous web that consists of lipid droplets and rearranged endoplasmic reticulum-derived membranes including single-, double- and multi-membrane vesicles. The double-membrane vesicles have been identified to contain NS3, NS5A, viral RNA and the autophagosomal marker microtubule-associated protein 1 light chain 3, corroborating the involvement of the autophagic pathway in the HCV life-cycle. In this review, we will highlight the crosstalk of the autophagosomal compartment with different steps of the HCV life-cycle and address its implications on favoring the survival of infected hepatocytes. PMID:26229393

  8. Hepatitis C Virus Treatment: Is It Possible To Cure All Hepatitis C Virus Patients?

    PubMed

    Muir, Andrew J; Naggie, Susanna

    2015-11-01

    The recent advances in hepatitis C virus (HCV) therapeutics have brought combinations of direct acting antiviral medications that offer interferon-free, well-tolerated regimens with sustained virologic response rates greater than 90% in clinical trials for many patient groups. The successes have prompted discussions regarding cure for all patients. These regimens have already demonstrated the ability to cure previously challenging patient groups, including human immunodeficiency virus-HCV coinfection, decompensated cirrhosis, and post-liver transplantation. Limitations exist in the current portfolio of agents, with suboptimal outcomes for genotype 3 and limited data in genotypes 5 and 6. More data are urgently needed in patients with chronic kidney disease and in children. With ongoing developments, highly effective regimens for all these patient groups are within reach. To deliver HCV treatment throughout the world and particularly in low- and middle-income countries, regimens need to be affordable but also pan-genotypic, well-tolerated, and delivered once daily for 4-8 weeks. With such a regimen, cure for all patients would then hinge on the ability to identify patients with HCV infection and deliver treatment within their communities. This review will discuss the strategies that will be necessary to realize this opportunity to cure all persons with HCV infection. PMID:26192145

  9. Differences in the detection of highly pathogenic avian influenza H5N1 virus in feather samples from 4-week-old and 24-week-old infected Pekin ducks (Anas platyrhynchos var. domestica).

    PubMed

    Aiello, Roberta; Beato, Maria Serena; Mancin, Marzia; Rigoni, Michela; Tejeda, Aurora Romero; Maniero, Silvia; Capua, Ilaria; Terregino, Calogero

    2013-08-30

    Previous studies have reported the detection of H5N1 HPAI virus in feathers from ducks naturally and experimentally infected and suggested that feather calami (FC) could be used as diagnostic samples for the early detection of H5N1 HPAI infections. Ducks are readily infected with H5N1 HPAI viruses although the development of clinical signs and deaths were reported as age-related with younger birds being more susceptible. The correlation between age and virus localisation in FC of infected ducks has not been studied to date. In the present study juvenile (4-week-old) and adult (24-week-old) Pekin ducks (Anas platyrhynchos var. domestica) were infected experimentally with a clade 2.2 H5N1 HPAI virus (A/duck/Nigeria/1071-23/2007). Tracheal (Tr) and cloacal (Cl) swabs and FC were collected at 3, 5, 7 and 10 days post infection and tested by RRT-PCR and a double antibody sandwich-ELISA (DAS-ELISA) developed in house. Virus was detected in swabs and FC of challenged ducks with a higher rate of detection in juvenile ducks. In this age group virus was detected over a longer period of time in FC compared to swabs. Our study showed that FC samples collected from young ducks are a valid diagnostic specimen for H5N1 HPAI virus detection. The DAS-ELISA on FC proved to be a suitable alternative diagnostic test when molecular and/or virus isolation techniques are not available therefore it could be useful in the diagnosis of H5N1 HPAI infections in under-resourced countries. PMID:23608476

  10. Absence of Active Hepatitis C Virus Infection in Human Immunodeficiency Virus Clinics in Zambia and Mozambique

    PubMed Central

    Wandeler, Gilles; Mulenga, Lloyd; Hobbins, Michael; Joao, Candido; Sinkala, Edford; Hector, Jonas; Aly, Musa; Chi, Benjamin H.; Egger, Matthias; Vinikoor, Michael J.

    2016-01-01

    Few studies have evaluated the prevalence of replicating hepatitis C virus (HCV) infection in sub-Saharan Africa. Among 1812 individuals infected with human immunodeficiency virus, no patient in rural Mozambique and 4 patients in urban Zambia were positive for anti-HCV antibodies. Of these, none had confirmed HCV replication. PMID:27047986

  11. Increasing Contact with Hepatitis E Virus in Red Deer, Spain

    PubMed Central

    Casas, Maribel; Martín, Marga; Vicente, Joaquín; Segalés, Joaquim; de la Fuente, José; Gortázar, Christian

    2010-01-01

    To describe the epidemiology of hepatitis E virus (HEV) in red deer in mainland Spain, we tested red deer for HEV RNA and antibodies. Overall, 10.4% and 13.6% of serum samples were positive by ELISA and reverse transcription–PCR, respectively. The increasing prevalence suggests a potential risk for humans. PMID:21122241

  12. New Hepatitis E Virus Genotype in Camels, the Middle East

    PubMed Central

    Lau, Susanna K.P.; Teng, Jade L.L.; Tsang, Alan K. L.; Joseph, Marina; Wong, Emily Y.M.; Tang, Ying; Sivakumar, Saritha; Xie, Jun; Bai, Ru; Wernery, Renate; Wernery, Ulrich; Yuen, Kwok-Yung

    2014-01-01

    In a molecular epidemiology study of hepatitis E virus (HEV) in dromedaries in Dubai, United Arab Emirates, HEV was detected in fecal samples from 3 camels. Complete genome sequencing of 2 strains showed >20% overall nucleotide difference to known HEVs. Comparative genomic and phylogenetic analyses revealed a previously unrecognized HEV genotype. PMID:24856611

  13. Wildlife Reservoir for Hepatitis E Virus, Southwestern France.

    PubMed

    Lhomme, Sebastien; Top, Sokunthea; Bertagnoli, Stephane; Dubois, Martine; Guerin, Jean-Luc; Izopet, Jacques

    2015-07-01

    Pigs are a reservoir for hepatitis E virus (HEV). To determine the relative contribution of game to the risk for human HEV infection in southwestern France, we tested wildlife samples. HEV RNA was in 3.3% of wildlife livers, indicating that in this region, eating game meat is as risky as eating pork. PMID:26079541

  14. Hepatitis E Virus Genotype 4 Outbreak, Italy, 2011

    PubMed Central

    Garbuglia, Anna R.; Scognamiglio, Paola; Petrosillo, Nicola; Mastroianni, Claudio Maria; Sordillo, Pasquale; Gentile, Daniele; La Scala, Patrizia; Girardi, Enrico

    2013-01-01

    During 2011, 5 persons in the area of Lazio, Italy were infected with a monophyletic strain of hepatitis E virus that showed high sequence homology with isolates from swine in China. Detection of this genotype in Italy parallels findings in other countries in Europe, signaling the possible spread of strains new to Western countries. PMID:23260079

  15. Hepatitis E virus antibodies in blood donors, France.

    PubMed

    Mansuy, Jean-Michel; Bendall, Richard; Legrand-Abravanel, Florence; Sauné, Karine; Miédouge, Marcel; Ellis, Vic; Rech, Henri; Destruel, François; Kamar, Nassim; Dalton, Harry R; Izopet, Jacques

    2011-12-01

    Using a validated sensitive assay, we found hepatitis E virus (HEV) IgG in 52.5% of voluntary blood donors in southwestern France. This finding suggests HEV is highly endemic to this region. The high HEV prevalence may reflect local dietary practices, such as eating uncooked pork and game products. PMID:22172156

  16. Wildlife Reservoir for Hepatitis E Virus, Southwestern France

    PubMed Central

    Lhomme, Sebastien; Top, Sokunthea; Bertagnoli, Stephane; Dubois, Martine; Guerin, Jean-Luc

    2015-01-01

    Pigs are a reservoir for hepatitis E virus (HEV). To determine the relative contribution of game to the risk for human HEV infection in southwestern France, we tested wildlife samples. HEV RNA was in 3.3% of wildlife livers, indicating that in this region, eating game meat is as risky as eating pork. PMID:26079541

  17. Hepatitis E Virus Genotype 3 in Humans and Swine, Bolivia

    PubMed Central

    Cavallo, Annalisa; Gonzales, José Luis; Bonelli, Sara Irene; Valda, Ybar; Pieri, Angela; Segundo, Higinio; Ibañez, Ramón; Mantella, Antonia; Bartalesi, Filippo; Tolari, Francesco; Bartoloni, Alessandro

    2011-01-01

    We determined the seroprevalence of hepatitis E virus (HEV) in persons in 2 rural communities in southeastern Bolivia and the presence of HEV in human and swine fecal samples. HEV seroprevalence was 6.3%, and HEV genotype 3 strains with high sequence homology were detected. PMID:21801630

  18. Hemato-biochemical and pathological changes on avian influenza in naturally infected domestic ducks in Egypt

    PubMed Central

    Mahmoud, Essam A.

    2015-01-01

    Aim: Few studies have been made in regard to avian influenza (AI) in ducks, thus the aim of this work was planned to investigate the hematological, biochemical, and pathological changes in domestic Egyptian ducks naturally infected with AI. Materials and Methods: 30 duck from private backyards 3-month-old 15 were clinically healthy (Group 1) and the other fifteen (Group 2) were naturally diseased with AI (H5N1). The disease was diagnosed by polymerase chain reaction as H5N1. Results: Duck showed cyanosis, subcutaneous edema of head and neck with nervous signs (torticollis). Hematological studies revealed a microcytic hypochromic anemia. Biochemical studies revealed a significant decrease in total protein, albumin and globulin concentration with significant increase of activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, Υ-glutamyl transpeptidase, lactic acid dehydrogenase and creatine phsphokinase. Prominent increase in creatinine and uric acid in addition to hypocalcemia and hyperphosphatemia were significantly detected in the infected ducks. Histopathological finding confirm these investigations. Conclusion: The highly pathogenic AIV (A/H5N1) became more severe infectious to ducks than before and causes nervous manifestations and blindness which were uncommon in ducks. Besides the significant increases of hepatic enzymes, brain, heart, and renal markers as a response to virus damage to these organs. PMID:27047014

  19. Detection of Pathogenic Viruses in Sewage Provided Early Warnings of Hepatitis A Virus and Norovirus Outbreaks

    PubMed Central

    Hellmér, Maria; Paxéus, Nicklas; Magnius, Lars; Enache, Lucica; Arnholm, Birgitta; Johansson, Annette; Bergström, Tomas

    2014-01-01

    Most persons infected with enterically transmitted viruses shed large amounts of virus in feces for days or weeks, both before and after onset of symptoms. Therefore, viruses causing gastroenteritis may be detected in wastewater, even if only a few persons are infected. In this study, the presence of eight pathogenic viruses (norovirus, astrovirus, rotavirus, adenovirus, Aichi virus, parechovirus, hepatitis A virus [HAV], and hepatitis E virus) was investigated in sewage to explore whether their identification could be used as an early warning of outbreaks. Samples of the untreated sewage were collected in proportion to flow at Ryaverket, Gothenburg, Sweden. Daily samples collected during every second week between January and May 2013 were pooled and analyzed for detection of viruses by concentration through adsorption to milk proteins and PCR. The largest amount of noroviruses was detected in sewage 2 to 3 weeks before most patients were diagnosed with this infection in Gothenburg. The other viruses were detected at lower levels. HAV was detected between weeks 5 and 13, and partial sequencing of the structural VP1protein identified three different strains. Two strains were involved in an ongoing outbreak in Scandinavia and were also identified in samples from patients with acute hepatitis A in Gothenburg during spring of 2013. The third strain was unique and was not detected in any patient sample. The method used may thus be a tool to detect incipient outbreaks of these viruses and provide early warning before the causative pathogens have been recognized in health care. PMID:25172863

  20. Pathobiology and Treatment of Hepatitis Virus-Related Thrombocytopenia

    PubMed Central

    Stasi, Roberto; Chia, Lian Wea; Kalkur, Pallavi; Lowe, Robert; Shannon, Muriel S.

    2009-01-01

    Thrombocytopenia is a well recognized complication of infections, including those from hepatotropic viruses. Thrombocytopenia may actually be the only manifestation of vital hepatitis, which should therefore be considered in the differential diagnosis of primary immune thrombocytopenia (ITP). The mechanisms of thrombocytopenia associated with viral hepatitis vary widely depending on the specific infectious agent and the severity of liver disease. Most of the studies have described thrombocytopenia in association with chronic hepatitis C virus (HCV) infection, the most common cause of chronic infection worldwide. Studies have shown that treatment of HCV infection often results in substantial improvement or complete recovery of the thrombocytopenia. In patients with thrombocytopenia associated with HCV-related chronic liver disease, the use of eltrombopag, a thrombopoietin receptor agonist, normalizes platelet levels thereby permitting the initiation of antiviral therapy. PMID:21415958

  1. [Amniocentesis and viral risk (hepatitis B, C virus and HIV)].

    PubMed

    Ducarme, G; Ceccaldi, P-F; Bernuau, J; Luton, D

    2009-10-01

    Very few studies have properly addressed to the risk of fetal hepatitis B (HBV), hepatitis C (HCV) or human immunodeficiency virus (HIV) infection through amniocentesis. For HBV, this risk is low. However, knowledge of the maternal hepatitis B e antigen status is valuable in the counselling of risks associated with amniocentesis. For HCV, the risk is not well known but cannot be excluded. For HIV, it seems rational to propose a viral test before amniocentesis for patients with contamination's risk and to postpone the sampling in cases with positive results in order to obtain an undetectable HIV-1 RNA viral load. For these reasons, it can be useful to analyse for each virus the benefit of amniocentesis and the risk of mother-to-infant transmission, and to inform the patient. PMID:19679409

  2. Hepatitis E virus infections in humans and animals.

    PubMed

    Song, Young-Jo; Park, Woo-Jung; Park, Byung-Joo; Lee, Joong-Bok; Park, Seung-Yong; Song, Chang-Seon; Lee, Nak-Hyung; Seo, Kun-Ho; Kang, Young-Sun; Choi, In-Soo

    2014-01-01

    Hepatitis E has traditionally been considered an endemic disease of developing countries. It generally spreads through contaminated water. However, seroprevalence studies have shown that hepatitis E virus (HEV) infections are not uncommon in industrialized countries. In addition, the number of autochthonous hepatitis E cases in these countries is increasing. Most HEV infections in developed countries can be traced to the ingestion of contaminated raw or undercooked pork meat or sausages. Several animal species, including pigs, are known reservoirs of HEV that transmit the virus to humans. HEVs are now recognized as an emerging zoonotic agent. In this review, we describe the general characteristics of HEVs isolated from humans and animals, the risk factors for human HEV infection, and the current status of human vaccine development. PMID:24427760

  3. Hepatitis E virus infections in humans and animals

    PubMed Central

    Song, Young-Jo; Park, Woo-Jung; Park, Byung-Joo; Lee, Joong-Bok; Park, Seung-Yong; Song, Chang-Seon; Lee, Nak-Hyung; Seo, Kun-Ho; Kang, Young-Sun

    2014-01-01

    Hepatitis E has traditionally been considered an endemic disease of developing countries. It generally spreads through contaminated water. However, seroprevalence studies have shown that hepatitis E virus (HEV) infections are not uncommon in industrialized countries. In addition, the number of autochthonous hepatitis E cases in these countries is increasing. Most HEV infections in developed countries can be traced to the ingestion of contaminated raw or undercooked pork meat or sausages. Several animal species, including pigs, are known reservoirs of HEV that transmit the virus to humans. HEVs are now recognized as an emerging zoonotic agent. In this review, we describe the general characteristics of HEVs isolated from humans and animals, the risk factors for human HEV infection, and the current status of human vaccine development. PMID:24427760

  4. Hepatitis E virus as an emerging zoonotic pathogen

    PubMed Central

    Park, Woo-Jung; Park, Byung-Joo; Ahn, Hee-Seop; Lee, Joong-Bok; Park, Seung-Yong; Song, Chang-Seon; Lee, Sang-Won; Yoo, Han-Sang

    2016-01-01

    Hepatitis E outbreaks are a serious public health concern in developing countries. The disease causes acute infections, primarily in young adults. The mortality rate is approximately 2%; however, it can exceed 20% in pregnant women in some regions in India. The causative agent, hepatitis E virus (HEV), has been isolated from several animal species, including pigs. HEV genotypes 3 and 4 have been isolated from both humans and animals, and are recognized as zoonotic pathogens. Seroprevalence studies in animals and humans indirectly suggest that HEV infections occur worldwide. The virus is primarily transmitted to humans via undercooked animal meats in developed countries. Moreover, transfusion- and transplantation-mediated HEV infections have recently been reported. This review summarizes the general characteristics of hepatitis E, HEV infection status in animals and humans, the zoonotic transmission modes of HEV, and HEV vaccine development status. PMID:27051334

  5. Differences between Pekin and Muscovy ducks in response to vaccination against HPAI H5N1 virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vaccination of domestic ducks against highly pathogenic avian influenza (HPAI) H5N1 has been done in Asia with mixed results. One of the observations from the field is that Muscovy ducks (Cairina moschata) respond differently to vaccination than other common domestic ducks (Anas sp.). The objectiv...

  6. Inadequate protection of ducks and geese against H5N1 high pathogenicity avian influenza virus by a single vaccination

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ducks and geese are an important sustainable food source in developing countries. Few studies have been conducted to test vaccine efficacy in either ducks or geese. This study was conducted to investigate whether a single vaccination could protect White Pekin ducks and White Chinese geese against ...

  7. Molecular mechanism of hepatitis B virus-induced hepatocarcinogenesis

    PubMed Central

    Tarocchi, Mirko; Polvani, Simone; Marroncini, Giada; Galli, Andrea

    2014-01-01

    Hepatitis B virus (HBV) infection is a global public health problem with approximately 2 billion people that have been exposed to the virus. HBV is a member of a family of small, enveloped DNA viruses called hepadnaviruses, and has a preferential tropism for hepatocytes of mammals and birds. Epidemiological studies have proved a strong correlation between chronic hepatitis B virus infection and the development of hepatocellular carcinoma (HCC). HCC is the fifth most common malignancy with about 700000 new cases each year, and more than 50% of them arise in HBV carriers. A large number of studies describe the way in which HBV can contribute to HCC development. Multiple mechanisms have been proposed, including the accumulation of genetic damage due to immune-mediated hepatic inflammation and the induction of oxidative stress. There is evidence of the direct effects of the viral proteins HBx and HBs on the cell biology. Integration of HBV-DNA into the human genome is considered an early event in the carcinogenic process and can induce, through insertional mutagenesis, the alteration of gene expression and chromosomal instability. HBV has also epigenetic effects through the modification of the genomic methylation status. Furthermore, the virus plays an important role in the regulation of microRNA expression. This review will summarize the many mechanisms involved in HBV-related liver carcinogenesis. PMID:25206269

  8. Cloning of hepatitis C virus genomes and their properties.

    PubMed

    Arima, T; Shimomura, H; Nakajima, T; Kanai, K; Nagashima, H; Tsuji, T

    1990-09-01

    A random primed lambda gt11-cDNA library was constructed from donors plasma presumably infected by blood-borne non-A, non-B hepatitis (hepatitis C:HC) agent and immunoscreened with serum pooled from patients with acute or chronic HC. Twelve lambda gt11-cDNA clones were isolated that was shown to encode antigens associated specifically with HC infection in Japan as well as in USA. Of these two, as well as another clone which is specific only to Japanese HC infection, have unique nucleotide sequences and were extensively studied. They are not derived from host DNA and have no homology to the sequences of known human viruses including hepatitis A, B and D viruses, Ebstein-Barr virus, coxsackievirus, immunodeficiency virus type 1 or Japanese encephalitis virus. These results suggest that they are derived from the genome of HC agent(s). In addition, of these, one clone seems to encode epitopes derived from both the core and the surface polypeptides of the agent. PMID:1699832

  9. Genomic Diversity of Hepatitis B Virus Infection Associated With Fulminant Hepatitis B Development

    PubMed Central

    Mina, Thomas; Amini-Bavil-Olyaee, Samad; Tacke, Frank; Maes, Piet; Van Ranst, Marc; Pourkarim, Mahmoud Reza

    2015-01-01

    Context: After five decades of Hepatitis B Virus (HBV) vaccine discovery, HBV is still a major public health problem. Due to the high genetic diversity of HBV and selective pressure of the host immune system, intra-host evolution of this virus in different clinical manifestations is a hot topic of research. HBV infection causes a range of clinical manifestations from acute to chronic infection, cirrhosis and hepatocellular carcinoma. Among all forms of HBV infection manifestations, fulminant hepatitis B infection possesses the highest fatality rate. Almost 1% of the acutely infected patients develop fulminant hepatitis B, in which the mortality rate is around 70%. Evidence Acquisition: All published papers deposited in Genbank, on the topic of fulminant hepatitis were reviewed and their virological aspects were investigated. In this review, we highlight the genomic diversity of HBV reported from patients with fulminant HBV infection. Results: The most commonly detected diversities affect regulatory motifs of HBV in the core and S region, indicating that these alterations may convert the virus to an aggressive strain. Moreover, mutations at T-cell and B-cell epitopes located in pre-S1 and pre-S2 proteins may lead to an immune evasion of the virus, likely favoring a more severe clinical course of infection. Furthermore, point and frame shift mutations in the core region increase the viral replication of HBV and help virus to evade from immune system and guarantee its persistence. Conclusions: Fulminant hepatitis B is associated with distinct mutational patterns of HBV, underlining that genomic diversity of the virus is an important factor determining its pathogenicity. PMID:26288637

  10. Pathogenesis by subviral agents: viroids and hepatitis delta virus.

    PubMed

    Flores, Ricardo; Owens, Robert A; Taylor, John

    2016-04-01

    The viroids of plants are the simplest known infectious genetic elements. They have RNA genomes of up to 400 nucleotides in length and no protein encoding capacity. Hepatitis delta virus (HDV), an infectious agent found only in humans co-infected with hepatitis B virus (HBV), is just slightly more complex, with an RNA genome of about 1700 nucleotides, and the ability to express just one small protein. Viroid and HDV RNAs share several features that include circular structure, compact folding, and replication via a rolling-circle mechanism. Both agents were detected because of their obvious pathogenic effects. Their simplicity demands a greater need than conventional RNA or DNA viruses to redirect host components for facilitating their infectious cycle, a need that directly and indirectly incites pathogenic effects. The mechanisms by which these pathogenic effects are produced are the topic of this review. In this context, RNA silencing mediates certain aspects of viroid pathogenesis. PMID:26897654

  11. Hepatitis E virus infection in the HIV-positive patient.

    PubMed

    Debes, Jose D; Pisano, Maria Belen; Lotto, Martin; Re, Viviana

    2016-07-01

    Hepatitis E virus (HEV) is a RNA virus that can cause hepatitis. In immunocompetent individuals, infection with HEV usually leads to asymptomatic seroconversion. However, in immunosuppressed patients, such as transplant recipients, HEV can develop into a chronic infection. Studies regarding the seroprevalence and clinical implications of HEV in patients infected with the human immunodeficiency virus (HIV) are conflicting. Levels of CD4 count in blood seem to be the most widely associated risk factor, while other factors such as meat consumption or proximity to animals are less clearly associated with HEV infection. Progression to chronicity, as well as extrahepatic manifestations of HEV seem rare in HIV, and the implications of HEV in liver disease progression are poorly understood in the HIV-infected. In this review we describe the epidemiology, risk factors, and clinical implications of HEV infection in individuals infected with HIV. PMID:27243210

  12. HDVDB: a data warehouse for hepatitis delta virus.

    PubMed

    Singh, Sarita; Gupta, Sunil Kumar; Nischal, Anuradha; Pant, Kamlesh Kumar; Seth, Prahlad Kishore

    2015-01-01

    Hepatitis Delta Virus (HDV) is an RNA virus and causes delta hepatitis in humans. Although a lot of data is available for HDV, but retrieval of information is a complicated task. Current web database 'HDVDB' provides a comprehensive web-resource for HDV. The database is basically concerned with basic information about HDV and disease caused by this virus, genome structure, pathogenesis, epidemiology, symptoms and prevention, etc. Database also supplies sequence data and bibliographic information about HDV. A tool 'siHDV Predict' to design the effective siRNA molecule to control the activity of HDV, is also integrated in database. It is a user friendly information system available at public domain and provides annotated information about HDV for research scholars, scientists, pharma industry people for further study. PMID:25786795

  13. Hepatitis E virus infection: Epidemiology and treatment implications

    PubMed Central

    Lee, Ga Young; Poovorawan, Kittiyod; Intharasongkroh, Duangnapa; Sa-nguanmoo, Pattaratida; Vongpunsawad, Sompong; Chirathaworn, Chintana; Poovorawan, Yong

    2015-01-01

    Hepatitis E virus (HEV) infection is now established as an emerging enteric viral hepatitis. Standard treatments in acute and chronic hepatitis E remain to be established. This study undertakes a review of the epidemiology, treatment implication and vaccine prevention from published literature. HEV infection is a worldwide public health problem and can cause acute and chronic hepatitis E. HEV genotypes 1 and 2 are primarily found in developing countries due to waterborne transmission, while the zoonotic potential of genotypes 3 and 4 affects mostly industrialized countries. An awareness of HEV transmission through blood donation, especially in the immunocompromised and solid organ transplant patients, merits an effective anti-viral therapy. There are currently no clear indications for the treatment of acute hepatitis E. Despite concerns for side effects, ribavirin monotherapy or in combination with pegylated interferon alpha for at least 3 mo appeared to show significant efficacy in the treatment of chronic hepatitis E. However, there are no available treatment options for specific patient population groups, such as women who are pregnant. Vaccination and screening of HEV in blood donors are currently a global priority in managing infection. New strategies for the treatment and control of hepatitis E are required for both acute and chronic infections, such as prophylactic use of medications, controlling large outbreaks, and finding acceptable antiviral therapy for pregnant women and other patient groups for whom the current options of treatment are not viable. PMID:26568916

  14. Hepatitis C virus: Promising discoveries and new treatments

    PubMed Central

    Bastos, Juliana Cristina Santiago; Padilla, Marina Aiello; Caserta, Leonardo Cardia; Miotto, Noelle; Vigani, Aline Gonzalez; Arns, Clarice Weis

    2016-01-01

    Despite advances in therapy, hepatitis C virus (HCV) infection remains an important global health issue. It is estimated that a significant part of the world population is chronically infected with the virus, and many of those affected may develop cirrhosis or liver cancer. The virus shows considerable variability, a characteristic that directly interferes with disease treatment. The response to treatment varies according to HCV genotype and subtype. The continuous generation of variants (quasispecies) allows the virus to escape control by antivirals. Historically, the combination of ribavirin and interferon therapy has represented the only treatment option for the disease. Currently, several new treatment options are emerging and are available to a large part of the affected population. In addition, the search for new substances with antiviral activity against HCV continues, promising future improvements in treatment. Researchers should consider the mutation capacity of the virus and the other variables that affect treatment success. PMID:27605875

  15. Hepatitis C virus: Promising discoveries and new treatments.

    PubMed

    Bastos, Juliana Cristina Santiago; Padilla, Marina Aiello; Caserta, Leonardo Cardia; Miotto, Noelle; Vigani, Aline Gonzalez; Arns, Clarice Weis

    2016-07-28

    Despite advances in therapy, hepatitis C virus (HCV) infection remains an important global health issue. It is estimated that a significant part of the world population is chronically infected with the virus, and many of those affected may develop cirrhosis or liver cancer. The virus shows considerable variability, a characteristic that directly interferes with disease treatment. The response to treatment varies according to HCV genotype and subtype. The continuous generation of variants (quasispecies) allows the virus to escape control by antivirals. Historically, the combination of ribavirin and interferon therapy has represented the only treatment option for the disease. Currently, several new treatment options are emerging and are available to a large part of the affected population. In addition, the search for new substances with antiviral activity against HCV continues, promising future improvements in treatment. Researchers should consider the mutation capacity of the virus and the other variables that affect treatment success. PMID:27605875

  16. Reactivation of hepatitis B virus during interferon-free therapy with daclatasvir and asunaprevir in patient with hepatitis B virus/hepatitis C virus co-infection.

    PubMed

    Takayama, Hiroki; Sato, Takeshi; Ikeda, Fusao; Fujiki, Shigeatsu

    2016-03-01

    Direct-acting antiviral agents (DAA) for hepatitis C virus (HCV) are not effective for hepatitis B virus (HBV), which may be suggestive of reactivation of anti-HBe hepatitis during interferon (IFN)-free DAA therapy in HBV/HCV co-infected patients with inactive HBV. A 69-year-old male patient was diagnosed with chronic hepatitis due to HBV/HCV co-infection with serum levels of alanine aminotransferase (ALT) of 94 U/L, HCV RNA of 4.2 log IU/mL and HBV DNA of 2.5 log copies/mL. HCV was thought to be responsible for the hepatitis activity because of low level of HBV core-related antigen (3.1 log U/mL). He was treated with combination therapy of daclatasvir and asunaprevir. Serum ALT gradually increased, and reached 237 U/L on day 43 in spite of undetectable HCV RNA. Serum HBV DNA was increasing to 7.0 log copies/mL at that time. The treatment was stopped due to suspicion of drug-induced liver injury and/or HBV reactivation. Administration of entecavir reduced HBV DNA levels, followed by improvement in ALT levels. This report proposes that close monitoring of HBV DNA during the anti-HCV DAA therapy and the commencement of anti-HBV therapy with nucleoside analogs after the increase of HBV DNA should be considered in patients with HBV/HCV co-infection. PMID:26297529

  17. New models of hepatitis E virus replication in human and porcine hepatocyte cell lines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hepatitis E virus (HEV) causes acute, enterically-transmitted hepatitis. It is associated with large epidemics in tropical and subtropical regions where it is endemic or with sporadic cases in non-endemic regions. Unlike other hepatitis viruses, HEV has several animal reservoirs. Phylogenetic studie...

  18. 9 CFR 113.202 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Canine Hepatitis and Canine Adenovirus...; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.202 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus. Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed...

  19. 9 CFR 113.202 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Canine Hepatitis and Canine Adenovirus...; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.202 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus. Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed...

  20. A novel linear neutralizing epitope of hepatitis E virus.

    PubMed

    Tang, Zi-Min; Tang, Ming; Zhao, Min; Wen, Gui-Ping; Yang, Fan; Cai, Wei; Wang, Si-Ling; Zheng, Zi-Zheng; Xia, Ning-Shao

    2015-07-01

    Hepatitis E virus (HEV) is a serious public health problem that causes acute hepatitis in humans and is primarily transmitted through fecal and oral routes. The major anti-HEV antibody responses are against conformational epitopes located in a.a. 459-606 of HEV pORF2. All reported neutralization epitopes are present on the dimer domain constructed by this peptide. While looking for a neutralizing monoclonal antibody (MAb)-recognized linear epitope, we found a novel neutralizing linear epitope (L2) located in a.a. 423-437 of pORF2. Moreover, epitope L2 is proved non-immunodominant in the HEV-infection process. Using the hepatitis B virus core protein (HBc) as a carrier to display this novel linear epitope, we show herein that this epitope could induce a neutralizing antibody response against HEV in mice and could protect rhesus monkeys from HEV infection. Collectively, our results showed a novel non-immunodominant linear neutralizing epitope of hepatitis E virus, which provided additional insight of HEV vaccine. PMID:26051517

  1. Ducks: the "Trojan horses" of H5N1 influenza.

    PubMed

    Kim, Jeong-Ki; Negovetich, Nicholas J; Forrest, Heather L; Webster, Robert G

    2009-07-01

    Wild ducks are the main reservoir of influenza A viruses that can be transmitted to domestic poultry and mammals, including humans. Of the 16 hemagglutinin (HA) subtypes of influenza A viruses, only the H5 and H7 subtypes cause highly pathogenic (HP) influenza in the natural hosts. Several duck species are naturally resistant to HP Asian H5N1 influenza viruses. These duck species can shed and spread virus from both the respiratory and intestinal tracts while showing few or no disease signs. While the HP Asian H5N1 viruses are 100% lethal for chickens and other gallinaceous poultry, the absence of disease signs in some duck species has led to the concept that ducks are the "Trojan horses" of H5N1 in their surreptitious spread of virus. An important unresolved issue is whether the HP H5N1 viruses are maintained in the wild duck population of the world. Here, we review the ecology and pathobiology of ducks infected with influenza A viruses and ducks' role in the maintenance and spread of HP H5N1 viruses. We also identify the key questions about the role of ducks that must be resolved in order to understand the emergence and control of pandemic influenza. It is generally accepted that wild duck species can spread HP H5N1 viruses, but there is insufficient evidence to show that ducks maintain these viruses and transfer them from one generation to the next. PMID:19627369

  2. Hepatitis C Virus Treatment: Is It Possible To Cure All Hepatitis C Virus Patients?

    PubMed Central

    Muir, Andrew J.; Naggie, Susanna

    2016-01-01

    The recent advances in hepatitis C virus (HCV) therapeutics have brought combinations of direct acting antiviral medications that offer interferon-free, well-tolerated regimens with sustained virologic response rates greater than 90% in clinical trials for many patient groups. The successes have prompted discussions regarding cure for all patients. These regimens have already demonstrated the ability to cure previously challenging patient groups, including human immunodeficiency virus–HCV coinfection, decompensated cirrhosis, and post-liver transplantation. Limitations exist in the current portfolio of agents, with suboptimal outcomes for genotype 3 and limited data in genotypes 5 and 6. More data are urgently needed in patients with chronic kidney disease and in children. With ongoing developments, highly effective regimens for all these patient groups are within reach. To deliver HCV treatment throughout the world and particularly in low-and middle-income countries, regimens need to be affordable but also pan-genotypic, well-tolerated, and delivered once daily for 4–8 weeks. With such a regimen, cure for all patients would then hinge on the ability to identify patients with HCV infection and deliver treatment within their communities. This review will discuss the strategies that will be necessary to realize this opportunity to cure all persons with HCV infection. PMID:26192145

  3. Current progress in development of hepatitis C virus vaccines.

    PubMed

    Liang, T Jake

    2013-07-01

    Despite major advances in the understanding and treatment of hepatitis C, a preventive vaccine remains elusive. The marked genetic diversity and multiple mechanisms of persistence of hepatitis C virus, combined with the relatively poor immune response of the infected host against the virus, are major barriers. The lack of robust and convenient model systems further hampers the effort to develop an effective vaccine. Advances in our understanding of virus-host interactions and protective immunity in hepatitis C virus infection provide an important roadmap to develop potent and broadly directed vaccine candidates targeting both humoral and cellular immune responses. Multiple approaches to generating and testing viral immunogens have met with variable success. Several candidates have advanced to clinical trials based on promising results in chimpanzees. The ultimate path to a successful preventive vaccine requires comprehensive evaluations of all aspects of protective immunity, innovative application of state-of-the-art vaccine technology and properly designed vaccine trials that can affirm definitive endpoints of efficacy. PMID:23836237

  4. Hepatitis E virus: An ancient hidden enemy in Latin America

    PubMed Central

    Fierro, Nora A; Realpe, Mauricio; Meraz-Medina, Tzintli; Roman, Sonia; Panduro, Arturo

    2016-01-01

    Hepatitis E virus (HEV) infection is a common cause of acute clinical hepatitis worldwide. HEV is an RNA-containing virus and the only member of the genus Hepevirus in the family Hepeviridae. Human HEV is classified into four genotypes widely distributed across the world. The virus is mainly transmitted via the fecal-oral route, and water-borne epidemics have become characteristic of hepatitis E in developing countries, including those in Latin America. The zoonotic potential of HEV is broadly recognized. Thus, there is an urgent need to re-evaluate virus transmission scenarios and to enforce epidemiological surveillance systems. Additionally, it is known that HEV infections, initially defined as self-limiting, can also take chronic courses in immunocompromised patients. Moreover, we recently reported a high seroprevalence of HEV in samples from cirrhotic patients with no other etiological agents present, suggesting the potential role of HEV in the development of chronic liver illness. In this review, HEV genomic variability, transmission, chronic infectious course, zoonotic potential and treatment are discussed. Focus is placed on the impact of HEV infection in Latin America, to support the development of specific control strategies and the handling of this important and typically imperceptible viral infection. PMID:26900289

  5. [IMMUNOPATHOGENESIS OF OCCULT INFECTION CAUSED BY HEPATITIS B VIRUS].

    PubMed

    Semenenko, T A; Suslov, A P

    2015-01-01

    The concept of occult infection caused by hepatitis B virus (HBV) is determined as the presence of HBV DNA in blood sera or liver with the absence of detectable HBsAg. The actuality of this problem is associated with the fact, that occult hepatitis B (OHB) can be transmitted during hemotransfusions, cause reactivation of chronic hepatitis B in immune compromised individuals, facilitate development of liver cirrhosis and hepatocellular carcinoma. Several different hypotheses of OHB immunopathogenesis have been proposed, including a low number of copies of HBV DNA, altered immune response of the macroorganism, genetic variability of the S gene, integration of viral DNA into host genome, infection of mononuclear cells of peripheral blood, presence of immune complexes that hide HBsAg, and interference by other viruses such as HCV and HIV. Molecular mechanisms of HBV virus in HBsAg-negative individuals are not fully understood, however, viral mutations seem a very significant factor. Approaches of OHB prophylaxis including use of a polyvalent vaccine, that allows vaccination against wild and mutant HBV viruses, are examined. PMID:26950999

  6. Parenterally transmitted non-A, non-B hepatitis: virus-specific antibody response patterns in hepatitis C virus-infected chimpanzees.

    PubMed

    Bradley, D W; Krawczynski, K; Ebert, J W; McCaustland, K A; Choo, Q L; Houghton, M A; Kuo, G

    1990-10-01

    An established chimpanzee model of parenterally-transmitted non-A, non-B hepatitis was used to define virus-specific immune response patterns in acutely and persistently infected animals. Serial bleedings were obtained from 23 chimpanzees that had been experimentally infected with an isolate of hepatitis C virus, originally recovered from contaminated lots of factor VIII (antihemophilic) materials. Sera were assayed for the presence of antihepatitis C virus by a newly developed radioimmunoassay procedure that incorporated recombinant DNA-expressed viral antigen as a reagent. Twenty-one of 23 hepatitis C virus infected animals were shown to acquire antihepatitis C virus, most within 2-8 weeks after the major peak of alanine aminotransferase activity. All chimpanzees with biochemical, electron microscopic, and histological evidence of chronic disease clearly acquired antibody; 14 of 16 animals observed through the acute phase of disease were also shown to acquire antibody. A booster effect or anamnestic response was noted in two chimpanzees (one of which was negative for antihepatitis C virus following the acute phase of disease) after challenge with hepatitis C virus. Antihepatitis C virus was not neutralizing, because some animals with high levels of antibody were also shown to have high titers of circulating hepatitis C virus. The development and maintenance of anti-hepatitis C virus appears to reflect concomitant virus replication and high potential for infectivity. PMID:1697546

  7. Molecular characterization of duck enteritis virus CHv strain UL49.5 protein and its colocalization with glycoprotein M

    PubMed Central

    Lin, Meng; Wang, Mingshu; Gao, Xinghong; Zhu, Dekang; Chen, Shun; Liu, Mafeng; Yin, Zhongqiong; Wang, Yin; Chen, Xiaoyue

    2014-01-01

    The UL49.5 gene of most herpesviruses is conserved and encodes glycoprotein N. However, the UL49.5 protein of duck enteritis virus (DEV) (pUL49.5) has not been reported. In the current study, the DEV pUL49.5 gene was first subjected to molecular characterization. To verify the predicted intracellular localization of gene expression, the recombinant plasmid pEGFP-C1/pUL49.5 was constructed and used to transfect duck embryo fibroblasts. Next, the recombinant plasmid pDsRed1-N1/glycoprotein M (gM) was produced and used for co-transfection with the pEGFP-C1/pUL49.5 plasmid to determine whether DEV pUL49.5 and gM (a conserved protein in herpesviruses) colocalize. DEV pUL49.5 was thought to be an envelope glycoprotein with a signal peptide and two transmembrane domains. This protein was also predicted to localize in the cytoplasm and endoplasmic reticulum with a probability of 66.7%. Images taken by a fluorescence microscope at different time points revealed that the DEV pUL49.5 and gM proteins were both expressed in the cytoplasm. Overlap of the two different fluorescence signals appeared 12 h after transfection and continued to persist until the end of the experiment. These data indicate a possible interaction between DEV pUL49.5 and gM. PMID:24690604

  8. Hepatitis B Virus and Hepatitis C Virus Infections in United States-Bound Refugees from Asia and Africa

    PubMed Central

    Mixson-Hayden, Tonya; Lee, Deborah; Ganova-Raeva, Lilia; Drobeniuc, Jan; Stauffer, William M.; Teshale, Eyasu; Kamili, Saleem

    2014-01-01

    The aim of this study was to determine the prevalence of active hepatitis B and C virus infections among refugees from various countries in Africa and Asia. Pre-admission serum samples collected during 2002–2007 from refugees originating from Bhutan (N = 755), Myanmar (N = 1076), Iraq (N = 1137), Laos (N = 593), Thailand (N = 622), and Somalia (N = 707) were tested for hepatitis B virus (HBV) DNA and hepatitis C virus (HCV) RNA. The HBV DNA (genotypes A, B, C, and G) was detected in 12.1% of samples negative for anti-HBs. Highest HBV prevalence was found among Hmong; lowest among Bhutanese. The HCV RNA (genotypes 1a, 1b, 1c, 3b, 6n, and 6m) was detected in 1.3% of the samples. Highest HCV prevalence was found among Hmong from Thailand; lowest among Iraqis. Screening specific refugee groups at high risk for viral hepatitis infections will identify infected individuals who could benefit from referral to care and treatment and prevent further transmissions. PMID:24732462

  9. Hepatitis B virus and hepatitis C virus infections in United States-bound refugees from Asia and Africa.

    PubMed

    Mixson-Hayden, Tonya; Lee, Deborah; Ganova-Raeva, Lilia; Drobeniuc, Jan; Stauffer, William M; Teshale, Eyasu; Kamili, Saleem

    2014-06-01

    The aim of this study was to determine the prevalence of active hepatitis B and C virus infections among refugees from various countries in Africa and Asia. Pre-admission serum samples collected during 2002-2007 from refugees originating from Bhutan (N = 755), Myanmar (N = 1076), Iraq (N = 1137), Laos (N = 593), Thailand (N = 622), and Somalia (N = 707) were tested for hepatitis B virus (HBV) DNA and hepatitis C virus (HCV) RNA. The HBV DNA (genotypes A, B, C, and G) was detected in 12.1% of samples negative for anti-HBs. Highest HBV prevalence was found among Hmong; lowest among Bhutanese. The HCV RNA (genotypes 1a, 1b, 1c, 3b, 6n, and 6m) was detected in 1.3% of the samples. Highest HCV prevalence was found among Hmong from Thailand; lowest among Iraqis. Screening specific refugee groups at high risk for viral hepatitis infections will identify infected individuals who could benefit from referral to care and treatment and prevent further transmissions. PMID:24732462

  10. Influenza-A Viruses in Ducks in Northwestern Minnesota: Fine Scale Spatial and Temporal Variation in Prevalence and Subtype Diversity

    PubMed Central

    Wilcox, Benjamin R.; Knutsen, Gregory A.; Berdeen, James; Goekjian, Virginia; Poulson, Rebecca; Goyal, Sagar; Sreevatsan, Srinand; Cardona, Carol; Berghaus, Roy D.; Swayne, David E.; Yabsley, Michael J.; Stallknecht, David E.

    2011-01-01

    Waterfowl from northwestern Minnesota were sampled by cloacal swabbing for Avian Influenza Virus (AIV) from July – October in 2007 and 2008. AIV was detected in 222 (9.1%) of 2,441 ducks in 2007 and in 438 (17.9%) of 2,452 ducks in 2008. Prevalence of AIV peaked in late summer. We detected 27 AIV subtypes during 2007 and 31 during 2008. Ten hemagglutinin (HA) subtypes were detected each year (i.e., H1, 3–8, and 10–12 during 2007; H1-8, 10 and 11 during 2008). All neuraminidase (NA) subtypes were detected during each year of the study. Subtype diversity varied between years and increased with prevalence into September. Predominant subtypes during 2007 (comprising ≥5% of subtype diversity) included H1N1, H3N6, H3N8, H4N6, H7N3, H10N7, and H11N9. Predominant subtypes during 2008 included H3N6, H3N8, H4N6, H4N8, H6N1, and H10N7. Additionally, within each HA subtype, the same predominant HA/NA subtype combinations were detected each year and included H1N1, H3N8, H4N6, H5N2, H6N1, H7N3, H8N4, H10N7, and H11N9. The H2N3 and H12N5 viruses also predominated within the H2 and H12 subtypes, respectively, but only were detected during a single year (H2 and H12 viruses were not detected during 2007 and 2008, respectively). Mallards were the predominant species sampled (63.7% of the total), and 531 AIV were isolated from this species (80.5% of the total isolates). Mallard data collected during both years adequately described the observed temporal and spatial prevalence from the total sample and also adequately represented subtype diversity. Juvenile mallards also were adequate in describing the temporal and spatial prevalence of AIV as well as subtype diversity. PMID:21931636

  11. Effect of swine hepatitis E virus on the livers of experimentally infected Mongolian gerbils by swine hepatitis E virus.

    PubMed

    Yang, Yifei; Shi, Ruihan; She, Ruiping; Soomro, Majid Hussain; Mao, Jingjing; Du, Fang; Zhao, Yue; Liu, Can

    2015-10-01

    Previous studies have shown that hepatitis E virus (HEV) can be transmitted between rats, pigs, cattle, rabbits, chicken, cats, and deer. Because wild and domestic rodents have anti-HEV antibodies, they are considered potential reservoirs of HEV. In the current study, Mongolian gerbils were experimentally infected with swine hepatitis E virus and the effects of this infection were investigated. After inoculation with HEV, the liver-to-body weight ratio increased at 7 dpi. Mongolian gerbils demonstrated significant increase (p<0.05) in Aspartate Transaminase (AST), alanine transaminase (ALT) and total bilirubin (T-BIL) concentrations in the sera, and HEV IgG was detected at 21 days post-inoculation (dpi). Real-time PCR revealed that the copies of HEV RNA in the liver were detected at 7 dpi, and peaked at 28 dpi at a concentration of 7.73 logs g(-1). Using both light and electron microscopy, hepatic lesions were observed in the HEV inoculated animals. In the experimental group, characteristic viral hepatitis lesions were prominent in the liver. HEV antigen was detected in the liver by immunohistochemistry, and HEV ORF3 antigen was detectable in liver by Western blot. These results clearly demonstrate that viral load of HEV in livers was dynamic, and ultrastructural hepatic injury in HEV infected Mongolian gerbils and anti-HEV IgG positive seroconversion were observed during infection. PMID:26093307

  12. Extra-hepatic replication and infection of hepatitis E virus in neuronal-derived cells.

    PubMed

    Drave, S A; Debing, Y; Walter, S; Todt, D; Engelmann, M; Friesland, M; Wedemeyer, H; Neyts, J; Behrendt, P; Steinmann, E

    2016-07-01

    Hepatitis E virus (HEV) is the causative agent of hepatitis E in humans and a member of the genus Orthohepevirus in the family Hepeviridae. Infection usually leads to acute hepatitis that can become fulminant, particularly among pregnant women and in patients with preexisting liver disease, or may evolve to a chronic state, especially in immunosuppressed individuals. HEV has been shown to produce a range of extra-hepatic manifestations including aplastic anaemia, acute thyroiditis, glomerulonephritis as well as neurological disorders such as Guillain-Barré syndrome, neuralgic amyotrophy and encephalitis. The pathogenesis of these neurological injuries remains largely unknown, and it is also uncertain whether or not HEV can directly infect neuronal cells. In this study, we investigated whether HEV is capable of completing the viral life cycle in human neuronal-derived cell lines such as neuroepithelioma (SK-N-MC), desmoplastic cerebellar medulloblastoma (DAOY), glioblastoma multiforme (DBTRG), glioblastoma astrocytoma (U-373 MG) and oligodendrocytic (M03.13) cells. Following transfection of these cells with HEV Gaussia luciferase reporter virus, all tested cell lines supported HEV RNA replication. Furthermore, extra- and intracellular viral capsid was detected by an HEV antigen ELISA as a marker for virus assembly and release. Permissiveness for HEV cell entry could be demonstrated for the oligodendrocytic cell line M03.13. In conclusion, these results indicate that HEV tropism is not restricted to the liver and HEV can potentially complete the full viral life cycle in neuronal-derived tissues explaining neurologic disorders during HEV infection. PMID:26891712

  13. Ferret hepatitis E virus infection induces acute hepatitis and persistent infection in ferrets.

    PubMed

    Li, Tian-Cheng; Yang, Tingting; Yoshizaki, Sayaka; Ami, Yasushi; Suzaki, Yuriko; Ishii, Koji; Kishida, Noriko; Shirakura, Masayuki; Asanuma, Hideki; Takeda, Naokazu; Wakita, Takaji

    2016-02-01

    Ferret hepatitis E virus (HEV), a novel hepatitis E virus, has been identified in ferrets. However, the pathogenicity of ferret HEV remains unclear. In the present study, we compared the HEV RNA-positivity rates and alanine aminotransferase (ALT) levels of 63 ferrets between before and after import from the US to Japan. We found that the ferret HEV-RNA positivity rates were increased from 12.7% (8/63) to 60.3% (38/63), and ALT elevation was observed in 65.8% (25/38) of the ferret HEV RNA-positive ferrets, indicating that ferret HEV infection is responsible for liver damage. From long term-monitoring of ferret HEV infection we determined that this infection in ferrets exhibits three patterns: sub-clinical infection, acute hepatitis, and persistent infection. The ALT elevation was also observed in ferret HEV-infected ferrets in a primary infection experiment. These results indicate that the ferret HEV infection induced acute hepatitis and persistent infection in ferrets, suggesting that the ferrets are a candidate animal model for immunological as well as pathological studies of hepatitis E. PMID:26790932

  14. Screening for Hepatitis B Virus Infection in Nonpregnant Adolescents and Adults

    MedlinePlus

    ... Task Force learned about the potential benefits and harms of hepatitis B screening: People who are at ... that slow down the virus). Potential Benefits and Harms of Hepatitis B Screening and Treatment The Task ...

  15. Wild-type and e antigen-minus hepatitis B viruses and course of chronic hepatitis.

    PubMed Central

    Brunetto, M R; Giarin, M M; Oliveri, F; Chiaberge, E; Baldi, M; Alfarano, A; Serra, A; Saracco, G; Verme, G; Will, H

    1991-01-01

    Using an oligonucleotide hybridization assay, we studied the clinical implication of wild-type hepatitis B virus (HBV) and a HBV mutant that is unable to secrete hepatitis B e antigen (HBeAg) because of a translational defect due to a stop codon in the pre-C region in 106 hepatitis B surface antigen-positive patients with chronic hepatitis B. Wild-type HBV was detected in 31 of 42 (73.8%) HBeAg-positive patients, whereas a mixed viral population was present in 10 (23.8%). Significant differences in the severity and outcome of liver disease were not observed in the two groups of patients. However, the emergence of HBeAg-minus HBV in wild-type HBV carriers was associated with an exacerbation of liver disease and was followed by the presence of antibodies against HBeAg (anti-HBe) in serum in 50% of the cases. In 61 of 64 (95.3%) anti-HBe-positive patients, HBeAg-minus HBV was the predominant virus: HBeAg-minus HBV was detected in 42 patients (65.6%), whereas both wild-type and HBeAg-minus HBV were present in 19 (29.7%). HBeAg-minus HBV was associated with a course of hepatitis characterized by flare-ups of liver cell necrosis interspersed with periods of asymptomatic HBV carriage (P less than 0.01). These data support the hypothesis that genetic heterogeneity of HBV significantly influences the course and outcome of chronic hepatitis B. Wild-type HBV secreting HBeAg induces immunologic tolerance and causes chronic infection. HBeAg-minus HBV might be unable to induce chronic infection without the helper function of wild-type HBV, but it appears to be more pathogenic. Once chronic infection is established, HBeAg-minus HBV variants may prevail and displace wild-type virus. Images PMID:2034663

  16. Protective Efficacy of Recombinant Turkey Herpes Virus (rHVT-H5) and Inactivated H5N1 Vaccines in Commercial Mulard Ducks against the Highly Pathogenic Avian Influenza (HPAI) H5N1 Clade 2.2.1 Virus.

    PubMed

    Kilany, Walid H; Safwat, Marwa; Mohammed, Samy M; Salim, Abdullah; Fasina, Folorunso Oludayo; Fasanmi, Olubunmi G; Shalaby, Azhar G; Dauphin, Gwenaelle; Hassan, Mohammed K; Lubroth, Juan; Jobre, Yilma M

    2016-01-01

    In Egypt, ducks kept for commercial purposes constitute the second highest poultry population, at 150 million ducks/year. Hence, ducks play an important role in the introduction and transmission of avian influenza (AI) in the Egyptian poultry population. Attempts to control outbreaks include the use of vaccines, which have varying levels of efficacy and failure. To date, the effects of vaccine efficacy has rarely been determined in ducks. In this study, we evaluated the protective efficacy of a live recombinant vector vaccine based on a turkey Herpes Virus (HVT) expressing the H5 gene from a clade 2.2 H5N1 HPAIV strain (A/Swan/Hungary/499/2006) (rHVT-H5) and a bivalent inactivated H5N1 vaccine prepared from clade 2.2.1 and 2.2.1.1 H5N1 seeds in Mulard ducks. A 0.3ml/dose subcutaneous injection of rHVT-H5 vaccine was administered to one-day-old ducklings (D1) and another 0.5ml/dose subcutaneous injection of the inactivated MEFLUVAC was administered at 7 days (D7). Four separate challenge experiments were conducted at Days 21, 28, 35 and 42, in which all the vaccinated ducks were challenged with 106EID50/duck of H5N1 HPAI virus (A/chicken/Egypt/128s/2012(H5N1) (clade 2.2.1) via intranasal inoculation. Maternal-derived antibody regression and post-vaccination antibody immune responses were monitored weekly. Ducks vaccinated at 21, 28, 35 and 42 days with the rHVT-H5 and MEFLUVAC vaccines were protected against mortality (80%, 80%, 90% and 90%) and (50%, 70%, 80% and 90%) respectively, against challenges with the H5N1 HPAI virus. The amount of viral shedding and shedding rates were lower in the rHVT-H5 vaccine groups than in the MEFLUVAC groups only in the first two challenge experiments. However, the non-vaccinated groups shed significantly more of the virus than the vaccinated groups. Both rHVT-H5 and MEFLUVAC provide early protection, and rHVT-H5 vaccine in particular provides protection against HPAI challenge. PMID:27304069

  17. Protective Efficacy of Recombinant Turkey Herpes Virus (rHVT-H5) and Inactivated H5N1 Vaccines in Commercial Mulard Ducks against the Highly Pathogenic Avian Influenza (HPAI) H5N1 Clade 2.2.1 Virus

    PubMed Central

    Kilany, Walid H.; Safwat, Marwa; Mohammed, Samy M.; Salim, Abdullah; Fasina, Folorunso Oludayo; Fasanmi, Olubunmi G.; Shalaby, Azhar G.; Dauphin, Gwenaelle; Hassan, Mohammed K.; Lubroth, Juan; Jobre, Yilma M.

    2016-01-01

    In Egypt, ducks kept for commercial purposes constitute the second highest poultry population, at 150 million ducks/year. Hence, ducks play an important role in the introduction and transmission of avian influenza (AI) in the Egyptian poultry population. Attempts to control outbreaks include the use of vaccines, which have varying levels of efficacy and failure. To date, the effects of vaccine efficacy has rarely been determined in ducks. In this study, we evaluated the protective efficacy of a live recombinant vector vaccine based on a turkey Herpes Virus (HVT) expressing the H5 gene from a clade 2.2 H5N1 HPAIV strain (A/Swan/Hungary/499/2006) (rHVT-H5) and a bivalent inactivated H5N1 vaccine prepared from clade 2.2.1 and 2.2.1.1 H5N1 seeds in Mulard ducks. A 0.3ml/dose subcutaneous injection of rHVT-H5 vaccine was administered to one-day-old ducklings (D1) and another 0.5ml/dose subcutaneous injection of the inactivated MEFLUVAC was administered at 7 days (D7). Four separate challenge experiments were conducted at Days 21, 28, 35 and 42, in which all the vaccinated ducks were challenged with 106EID50/duck of H5N1 HPAI virus (A/chicken/Egypt/128s/2012(H5N1) (clade 2.2.1) via intranasal inoculation. Maternal-derived antibody regression and post-vaccination antibody immune responses were monitored weekly. Ducks vaccinated at 21, 28, 35 and 42 days with the rHVT-H5 and MEFLUVAC vaccines were protected against mortality (80%, 80%, 90% and 90%) and (50%, 70%, 80% and 90%) respectively, against challenges with the H5N1 HPAI virus. The amount of viral shedding and shedding rates were lower in the rHVT-H5 vaccine groups than in the MEFLUVAC groups only in the first two challenge experiments. However, the non-vaccinated groups shed significantly more of the virus than the vaccinated groups. Both rHVT-H5 and MEFLUVAC provide early protection, and rHVT-H5 vaccine in particular provides protection against HPAI challenge. PMID:27304069

  18. The pathogenicity of H7 subtype avian influenza viruses in chickens, turkeys and ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza (AI) viruses infect numerous avian species, and low pathogenicity (LP) AI viruses of the H7 subtype are typically reported to produce mild or subclinical infections in both wild aquatic birds and domestic poultry. However relatively little work has been done to compare LPAI viruses ...

  19. Susceptibility of wood ducks (Aix sponsa) to H5N1 highly pathogenic avian influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Since 2002, H5N1 highly pathogenic avian influenza (HPAI) viruses have caused mortality in numerous species of wild birds. Although these infections document the susceptibility of wild birds to H5N1 HPAI viruses and the spillover of these viruses from infected domestic birds to wild birds, it is un...

  20. Experimental co-infection studies with avian influenza viruses and Newcastle Disease viruses in chickens, turkeys and domestic ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Co-infections of poultry with Newcastle Disease viruses (NDVs) and Avian Influenza viruses (AIVs) present a problem both from the clinical point of view and the diagnosis of these viruses. Little has been done to understand the interactions between these two viruses when infecting poultry. Exposur...

  1. Border Control in Hepatitis C Virus Infection: Inhibiting Viral Entry.

    PubMed

    Schweitzer, Cameron J; Liang, T Jake

    2015-09-11

    A new era has begun in the treatment of hepatitis C virus (HCV) infection with powerful yet expensive therapies. New treatments are emerging that target the entry step of HCV and could potentially block reinfection after liver transplant. These treatments include antibodies, which target the virus or host receptors required by HCV. Additionally, several new and previously approved small-molecule compounds have been described that target unique aspects of HCV entry. Overall, the blocking entry represents an attractive strategy that could yield powerful combination therapies to combat HCV. PMID:27617924

  2. Proposed reference sequences for hepatitis E virus subtypes.

    PubMed

    Smith, Donald B; Simmonds, Peter; Izopet, Jacques; Oliveira-Filho, Edmilson F; Ulrich, Rainer G; Johne, Reimar; Koenig, Matthias; Jameel, Shahid; Harrison, Tim J; Meng, Xiang-Jin; Okamoto, Hiroaki; Van der Poel, Wim H M; Purdy, Michael A

    2016-03-01

    The nomenclature of hepatitis E virus (HEV) subtypes is inconsistent and makes comparison of different studies problematic. We have provided a table of proposed complete genome reference sequences for each subtype. The criteria for subtype assignment vary between different genotypes and methodologies, and so a conservative pragmatic approach has been favoured. Updates to this table will be posted on the International Committee on Taxonomy of Viruses website (http://talk.ictvonline.org/r.ashx?C). The use of common reference sequences will facilitate communication between researchers and help clarify the epidemiology of this important human pathogen. This subtyping procedure might be adopted for other taxa of the genus Orthohepevirus. PMID:26743685

  3. Chemokine antagonism in chronic hepatitis C virus infection.

    PubMed

    Charles, Edgar D; Dustin, Lynn B

    2011-01-01

    Immune responses to hepatitis C virus (HCV) fail to clear the virus in most individuals. Why patients who are less likely to clear HCV infection have high plasma levels of CXCL10 (also known as IP-10), a chemokine that directs T cells to sites of infection, has long been unclear. In this issue of the JCI, Casrouge and colleagues shed light on this paradox by showing that CXCL10 in the plasma of many HCV patients is enzymatically processed to produce a CXCL10 receptor antagonist. These findings introduce a role for chemokine antagonism during HCV infection and unveil new avenues for improved HCV diagnosis and therapy. PMID:21183783

  4. Recent insights into hepatitis B virus-host interactions.

    PubMed

    Ezzikouri, Sayeh; Ozawa, Makoto; Kohara, Michinori; Elmdaghri, Naima; Benjelloun, Soumaya; Tsukiyama-Kohara, Kyoko

    2014-06-01

    Hepatitis B virus (HBV) poses a threat to global public health mainly because of complications of HBV-related chronic liver disease. HBV exhibits a narrow host range, replicating primarily in hepatocytes by a still poorly understood mechanism. For the generation of progeny virions, HBV depends on interactions with specific host factors through its life cycle. Revealing and characterizing these interactions are keys to identifying novel antiviral targets, and to developing specific treatment strategies for HBV patients. In this review, recent insights into the HBV-host interactions, especially on virus entry, intracellular trafficking, genome transcription and replication, budding and release, and even cellular restriction factors were reviewed. PMID:24604126

  5. Hepatitis B virus large surface protein: function and fame

    PubMed Central

    Churin, Yuri; Roderfeld, Martin

    2015-01-01

    Chronic infection with hepatitis B virus (HBV) is the leading cause of liver cirrhosis and hepatocellular carcinoma worldwide. HBV life cycle begins with viral attachment to hepatocytes, mediated by the large HBV surface protein (LHBs). Identification of the sodium-taurocholate cotransporting polypeptide (NTCP) as a HBV receptor has revealed a suitable target for viral entry inhibition. Analysis of serum hepatitis B surface antigen (HBsAg) level is a non-invasive diagnostic parameter that improves HBV treatment opportunities. Furthermore, HBsAg plays an important role in manipulation of host immune response by HBV. However, observations in patients with chronic hepatitis B under conditions of immune suppression and in transgenic mouse models of HBV infection suggest, that in absence of adaptive immune responses cellular mechanisms induced by HBV may also lead to the development of liver diseases. Thus, the multifaceted pathological aspects of HBsAg predetermine the design of new therapeutical options modulating associated biological implications. PMID:25713800

  6. Hepatitis B virus large surface protein: function and fame.

    PubMed

    Churin, Yuri; Roderfeld, Martin; Roeb, Elke

    2015-02-01

    Chronic infection with hepatitis B virus (HBV) is the leading cause of liver cirrhosis and hepatocellular carcinoma worldwide. HBV life cycle begins with viral attachment to hepatocytes, mediated by the large HBV surface protein (LHBs). Identification of the sodium-taurocholate cotransporting polypeptide (NTCP) as a HBV receptor has revealed a suitable target for viral entry inhibition. Analysis of serum hepatitis B surface antigen (HBsAg) level is a non-invasive diagnostic parameter that improves HBV treatment opportunities. Furthermore, HBsAg plays an important role in manipulation of host immune response by HBV. However, observations in patients with chronic hepatitis B under conditions of immune suppression and in transgenic mouse models of HBV infection suggest, that in absence of adaptive immune responses cellular mechanisms induced by HBV may also lead to the development of liver diseases. Thus, the multifaceted pathological aspects of HBsAg predetermine the design of new therapeutical options modulating associated biological implications. PMID:25713800

  7. Analysis of a successful immune response against hepatitis C virus.

    PubMed

    Cooper, S; Erickson, A L; Adams, E J; Kansopon, J; Weiner, A J; Chien, D Y; Houghton, M; Parham, P; Walker, C M

    1999-04-01

    To investigate the type of immunity responsible for resolution of hepatitis C virus (HCV) infection, we monitored antibody and intrahepatic cytotoxic T lymphocyte (CTL) responses during acute (<20 weeks) infection in chimpanzees. Two animals who terminated infection made strong CTL but poor antibody responses. In both resolvers, CTL targeted at least six viral regions. In contrast, animals developing chronic hepatitis generated weaker acute CTL responses. Extensive analysis of the fine specificity of the CTL in one resolver revealed nine peptide epitopes and restriction by all six MHC class I allotypes. Every specificity shown during acute hepatitis persisted in normal liver tissue more than 1 yr after resolution. These results suggest that CD8+CTL are better correlated with protection against HCV infection than antibodies. PMID:10229187

  8. Fulminant hepatitis following primary herpes simplex virus infection.

    PubMed

    Al Midani, A; Pinney, J; Field, N; Atkinson, C; Haque, T; Harber, M

    2011-01-01

    Fulminant hepatic failure (FHF) is a rare but well-recognized complication of primary herpes simplex virus (HSV) infection in immunocompromised patients. Here, we report two cases of acute hepatitis and FHF secondary to primary HSV type 1 infection following renal transplantation in the absence of any mucocutaneous manifestation. High levels of HSV type-1 DNA were detected in the blood. Both patients were seronegative for HSV 1 and HSV 2 immunoglobulin G (IgG) before transplantation, whereas the donor of patient 1 was HSV 1 IgG-positive but had no viremia and the donor of patient 2 was HSV-seronegative. Patient 1 recovered with acyclovir and immunoglobulin whereas patient 2 did not respond and succumbed to death. HSV-seronegative patients are potentially at risk of developing severe primary HSV disease following transplantation, particularly in the absence of routine anti-viral prophylaxis. HSV infection should always be excluded in transplant patients with hepatic dysfunction. PMID:21196623

  9. Genetic variation of occult hepatitis B virus infection

    PubMed Central

    Zhu, Hui-Lan; Li, Xu; Li, Jun; Zhang, Zhen-Hua

    2016-01-01

    Occult hepatitis B virus infection (OBI), characterized as the persistence of hepatitis B virus (HBV) surface antigen (HBsAg) seronegativity and low viral load in blood or liver, is a special form of HBV infection. OBI may be related mainly to mutations in the HBV genome, although the underlying mechanism of it remains to be clarified. Mutations especially within the immunodominant “α” determinant of S protein are “hot spots” that could contribute to the occurrence of OBI via affecting antigenicity and immunogenicity of HBsAg or replication and secretion of virion. Clinical reports account for a large proportion of previous studies on OBI, while functional analyses, especially those based on full-length HBV genome, are rare. PMID:27053845

  10. Hepatitis B virus infection and primary hepatocellular carcinoma.

    PubMed Central

    Feitelson, M

    1992-01-01

    For many years, epidemiological studies have demonstrated a strong link between chronic hepatitis B virus (HBV) infection and the development of primary hepatocellular carcinoma (PHC). Other hepatocarcinogens such as hepatitis C virus and aflatoxin also contribute to hepatocarcinogenesis either in conjunction with HBV infection or alone. Cellular and molecular biological studies are providing explanations for the HBV-PHC relationship, and models are now being formulated to further test the relative importance of various factors such as viral DNA integration, activation of oncogenes, genetic instability, loss of tumor suppressor genes, and trans-activating properties of HBV to the pathogenesis of PHC. Further research will probably define more than a single mechanism whereby chronic HBV infection results in PHC. PMID:1323384

  11. Current treatments for chronic hepatitis B virus infections.

    PubMed

    Zoulim, Fabien; Lebossé, Fanny; Levrero, Massimo

    2016-06-01

    Over 240 million people worldwide are chronically infected with hepatitis B virus (HBV) and although a prophylactic vaccine and effective antiviral therapies are available, no cure exists. Curative regimens are urgently needed because up to one million deaths per year are caused by HBV-related liver cancer and end-stage liver disease. HBV is an hepatotropic virus which belongs to the Hepadnaviridae family and replicates its DNA genome via a reverse transcriptase mechanism. Effective therapies have been developed for chronic hepatitis B (CHB) infection in the last two decades. They rely on the use of interferon alpha and its pegylated formulation, and on nucleos(t)ide analogs that inhibit viral polymerase activity. Their results are discussed in this review as well as future perspectives. PMID:27318098

  12. Update on hepatitis B and C virus diagnosis

    PubMed Central

    Villar, Livia Melo; Cruz, Helena Medina; Barbosa, Jakeline Ribeiro; Bezerra, Cristianne Sousa; Portilho, Moyra Machado; Scalioni, Letícia de Paula

    2015-01-01

    Viral hepatitis B and C virus (HBV and HCV) are responsible for the most of chronic liver disease worldwide and are transmitted by parenteral route, sexual and vertical transmission. One important measure to reduce the burden of these infections is the diagnosis of acute and chronic cases of HBV and HCV. In order to provide an effective diagnosis and monitoring of antiviral treatment, it is important to choose sensitive, rapid, inexpensive, and robust analytical methods. Primary diagnosis of HBV and HCV infection is made by using serological tests for detecting antigens and antibodies against these viruses. In order to confirm primary diagnosis, to quantify viral load, to determine genotypes and resistance mutants for antiviral treatment, qualitative and quantitative molecular tests are used. In this manuscript, we review the current serological and molecular methods for the diagnosis of hepatitis B and C. PMID:26568915

  13. Hepatic Cells Derived from Induced Pluripotent Stem Cells of Pigtail Macaques Support Hepatitis C Virus infection

    PubMed Central

    Sourisseau, Marion; Goldman, Orit; He, Wenqian; Gori, Jennifer L.; Kiem, Hans-Peter; Gouon-Evans, Valerie; Evans, Matthew J.

    2013-01-01

    The narrow species tropism of hepatitis C virus (HCV) limits animal studies. We found that pigtail macaque (Macaca nemestrina) hepatic cells derived from induced pluripotent stem cells support the entire HCV life cycle, although infection efficiency was limited by defects in the HCV cell entry process. This block was overcome by either increasing occludin expression, complementing the cells with human CD81, or infecting them with a strain of HCV with less-restricted requirements for CD81. Using this system, we can modify viral and host cell genetics to make pigtail macaques a suitable, clinically relevant model for the study of HCV infection. PMID:23891978

  14. Hepatitis E Virus Superinfection and Clinical Progression in Hepatitis B Patients

    PubMed Central

    Hoan, Nghiem Xuan; Tong, Hoang Van; Hecht, Nicole; Sy, Bui Tien; Marcinek, Patrick; Meyer, Christian G.; Song, Le Huu; Toan, Nguyen Linh; Kurreck, Jens; Kremsner, Peter G.; Bock, C-Thomas; Velavan, Thirumalaisamy P.

    2015-01-01

    Hepatitis E virus (HEV) infection may cause acute hepatitis and lead to hepatic failure in developing and developed countries. We studied HEV seroprevalences in patients with hepatitis B virus (HBV) infection to understand the consequences of HEV superinfection in a Vietnamese population. This cross-sectional study was conducted from 2012 to 2013 and included 1318 Vietnamese patients with HBV-related liver diseases and 340 healthy controls. The case group included patients with acute (n = 26) and chronic hepatitis B (n = 744), liver cirrhosis (n = 160), hepatocellular carcinoma (n = 166) and patients with both liver cirrhosis and hepatocellular carcinoma (n = 222). Anti-HEV IgG and IgM antibodies were assessed in patients and controls by ELISA. HEV-RNA was identified by PCR assays and sequencing. Seroprevalences of anti-HEV IgG among hepatitis B patients and controls were 45% and 31%, respectively (adjusted P = 0.034). Anti-HEV IgM seroprevalences were 11.6% and 4.7% in patients and controls, respectively (adjusted P = 0.005). Seroprevalences were higher among the elder individuals. When stratifying for patient groups, those with liver cirrhosis had the highest anti-HEV IgG (52%) and anti-HEV IgM (19%) seroprevalences. Hepatitis B patients with current HEV infection had abnormal liver function tests compared to patients with past or without HEV infection. One HEV isolate was retrieved from a patient with both liver cirrhosis and hepatocellular carcinoma and identified as HEV genotype 3. This study indicates high prevalences of HEV infection in Vietnamese HBV patients and among healthy individuals and shows that HEV superinfection may influence the outcome and progression of HBV-related liver disease. PMID:26844288

  15. Host-virus interactions in hepatitis B and hepatitis C infection.

    PubMed

    Yoshio, Sachiyo; Kanto, Tatsuya

    2016-05-01

    Hepatitis B virus (HBV) and hepatitis C virus (HCV) are among the most endemic pathogens worldwide, with more than 500 million people globally currently infected with these viruses. These pathogens can cause acute and chronic hepatitis that progress to liver cirrhosis or hepatocellular carcinoma. Both viruses utilize multifaceted strategies to evade the host surveillance system and fall below the immunological radar. HBV has developed specific strategies to evade recognition by the innate immune system and is acknowledged to be a stealth virus. However, extensive research has revealed that HBV is recognized by dendritic cells (DCs) and natural killer (NK) cells. Indoleamine-2, 3-dioxygenase is an enforcer of sequential immune reactions in acute hepatitis B, and this molecule has been shown to be induced by the interaction of HBV-infected hepatocytes, DCs, and NK cells. The interleukin-28B genotype has been reported to influence HCV eradication either therapeutically or spontaneously, but the biological function of its gene product, a type-III interferon (IFN-λ3), remains to be elucidated. Human BDCA3(+)DCs have also been shown to be a potent producer of IFN-λ3 in HCV infection, suggesting the possibility that BDCA3(+)DCs could play a key role in developing therapeutic HCV vaccine. Here we review the current state of research on immune responses against HBV and HCV infection, with a specific focus on innate immunity. A comprehensive study based on clinical samples is urgently needed to improve our understanding of the immune mechanisms associated with viral control and thus to develop novel immune modulatory therapies to cure chronic HBV and HCV infection. PMID:26894594

  16. Prevalence of Hepatitis B Virus Infection in Kenya, 2007.

    PubMed

    Ly, Kathleen N; Kim, Andrea A; Umuro, Mamo; Drobenuic, Jan; Williamson, John M; Montgomery, Joel M; Fields, Barry S; Teshale, Eyasu H

    2016-08-01

    Current estimates put the prevalence of hepatitis B virus (HBV) infection in Kenya at 5-8%. We determined the HBV infection prevalence in the human immunodeficiency virus (HIV)-negative Kenyan adult and adolescent population based on samples collected from a national survey. We analyzed data from HIV-negative participants in the 2007 Kenya AIDS Indicator Survey to estimate the HBV infection prevalence. We defined past or present HBV infection as presence of total hepatitis B core antibody (HBcAb), and chronic HBV infection (CHBI) as presence of both total HBcAb and hepatitis B surface antigen (HBsAg). We calculated crude and adjusted odds of HBV infection by demographic characteristics and risk factors using logistic regression analyses. Of 1,091 participants aged 15-64 years, approximately 31.5% (95% confidence interval [CI] = 28.0-35.3%) had exposure to HBV, corresponding to approximately 6.1 million (CI = 5.4-6.8 million) with past or present HBV infection. The estimated prevalence of CHBI was 2.1% (95% CI = 1.4-3.1%), corresponding to approximately 398,000 (CI = 261,000-602,000) with CHBI. CHBI is a major public health problem in Kenya, affecting approximately 400,000 persons. Knowing the HBV infection prevalence at baseline is important for planning and public health policy decision making and for monitoring the impact of viral hepatitis prevention programs. PMID:27273644

  17. An outbreak of duck viral enteritis (duck plague) in domestic Muscovy ducks (Cairina moschata domesticus) in Illinois.

    PubMed

    Campagnolo, E R; Banerjee, M; Panigrahy, B; Jones, R L

    2001-01-01

    Duck viral enteritis (DVE) was diagnosed in an outbreak of the disease in a resident population of Muscovy ducks (Cairina moschata domesticus) on a privately owned multispecies game bird production facility in Illinois, where it claimed 625 ducks. This disease condition had not been reported previously in domestic ducks in Illinois. Although other varieties and age groups of domestic waterfowl (i.e., black ducks, rhumen ducks, Pekin ducks, ducklings, and geese) were present on the game bird farm, the morbidity and mortality (100%) in this epornitic was solely limited to adult ducks of the Muscovy lineage. The clinical signs in the affected ducks were lethargy, diarrhea, dehydration, and death within 2-3 hr of onset of symptoms. Gross pathologic changes were nonspecific and included ecchymotic hemorrhage, effusion of fluid and blood within body cavities reflective of an acute systemic infectious disease. Light microscopic findings were necrosis of primarily digestive lining epithelium and variable lymphohistiocytic infiltration within mucosal and serosal connective tissues. Intranuclear inclusions resembling characteristic herpetic (i.e., Cowdry type A) inclusions were observed primarily in the digestive, respiratory, and reproductive tracts; liver; and spleen. Esophageal candidiasis, bacteriosis, and systemic Pasteurella anatipestifer infections, thought to be concurrent or opportunistic infections, were present in several ducks. DVE virus was demonstrated in infected Muscovy duck embryo fibroblast cells by direct DVE virus-specific fluorescent antibody staining. PMID:11417839

  18. ACQUISITION OF ANTIBODIES TO VARIOUS COXSACKIE AND ECHO VIRUSES AND HEPATITIS A VIRUS IN AGRICULTURAL COMMUNAL SETTLEMENTS IN ISRAEL

    EPA Science Inventory

    A seroepidemiological study was conducted to measure the antibody prevalence for eight different enteric viruses. These include seven 'classical' enteroviruses, ie, Coxsackie virus types A9, B1, B3, B4 and three ECHO virus types 4,7, and 9, as well as hepatitis A virus (HAV), rec...

  19. Selective Hepatitis B Virus Vaccination Has Reduced Hepatitis B Virus Transmission in The Netherlands

    PubMed Central

    Koedijk, Femke; van Ballegooijen, Marijn; Cremer, Jeroen; Bruisten, Sylvia; Coutinho, Roel

    2013-01-01

    Background & Aims In the Netherlands, a selective hepatitis B virus (HBV) vaccination programme started in 2002 for men having sex with men, drug users, commercial sex workers and heterosexuals with frequent partner changes. We assessed the programme's effectiveness to guide policy on HBV prevention. Methods We analysed reports of acute HBV infection in the Netherlands between 2004 and 2010 requesting serum from patients for HBV-genome S- and C-region sequencing. We used coalescence analyses to assess genetic diversity of nonimported genotype-A cases over time. Results 1687 patients with acute HBV infection were reported between 2004 and 2010. The incidence of reported acute HBV infection decreased from 1.8 to 1.2 per 100,000 inhabitants, mostly due to a reduction in the number of cases in men who have sex with men. Men were overrepresented among cases with an unknown route of transmission, especially among genotype A2 cases mainly associated with transmission through male homosexual contact. The genetic diversity of nonimported genotype-A strains obtained from men who have sex with men decreased from 2006 onwards, suggesting HBV incidence in this group decreased. Conclusions The selective HBV-vaccination programme for behavioural high-risk groups very likely reduced the incidence of HBV infection in the Netherlands mainly by preventing HBV infections in men who have sex with men. A considerable proportion of cases in men who did not report risk behaviour was probably acquired through homosexual contact. Our findings support continuation of the programme, and adopting similar approaches in other countries where HBV transmission is focused in high-risk adults. PMID:23922651

  20. New antiviral targets for innovative treatment concepts for hepatitis B virus and hepatitis delta virus.

    PubMed

    Durantel, David; Zoulim, Fabien

    2016-04-01

    Current therapies of chronic hepatitis B (CHB) remain limited to pegylated-interferon-alpha (PegIFN-α) or any of the five approved nucleos(t)ide analogues (NUC) treatments. While viral suppression can be achieved in the majority of patients with the high-barrier-to-resistance new-generation of NUC, i.e. entecavir and tenofovir, HBsAg loss is achieved by PegIFN-α and/or NUC in only 10% of patients, after a 5-year follow-up. Attempts to improve the response by administering two different NUC or a combination of NUC and PegIFN-α have not provided a dramatic increase in the rate of functional cure. Because of this and the need of long-term NUC administration, there is a renewed interest regarding the understanding of various steps of the HBV replication cycle, as well as specific virus-host cell interactions, in order to define new targets and develop new antiviral drugs. This includes a direct inhibition of viral replication with entry inhibitors, drugs targeting cccDNA, siRNA targeting viral transcripts, capsid assembly modulators, and approaches targeting the secretion of viral envelope proteins. Restoration of immune responses is a complementary approach. The restoration of innate immunity against HBV can be achieved, with TLR agonists or specific antiviral cytokine delivery. Restoration of adaptive immunity may be achieved with inhibitors of negative checkpoint regulators, therapeutic vaccines, or autologous transfer of engineered HBV-specific T cells. Novel targets and compounds will readily be evaluated using both relevant and novel in vitro and in vivo models of HBV infection. The addition of one or several new drugs to current therapies should offer the prospect of a markedly improved response to treatments and an increased rate of functional cure. This should lead to a reduced risk of antiviral drug resistance, and to a decreased incidence of cirrhosis and hepatocellular carcinoma (HCC). PMID:27084032

  1. Mechanisms of Methods for Hepatitis C Virus Inactivation

    PubMed Central

    Pfaender, Stephanie; Brinkmann, Janine; Todt, Daniel; Riebesehl, Nina; Steinmann, Joerg; Steinmann, Jochen; Pietschmann, Thomas

    2014-01-01

    Virus inactivation by chemical disinfectants is an important instrument for infection control in medical settings, but the mechanisms involved are poorly understood. In this study, we systematically investigated the effects of several antiviral treatments on hepatitis C virus (HCV) particles as model for enveloped viruses. Studies were performed with authentic cell culture-derived viruses, and the influence of chemical disinfectants, heat, and UV treatment on HCV was analyzed by the determination of infectious particles in a limiting-dilution assay, by quantitative reverse transcription-PCR, by core enzyme-linked immunosorbent assay, and by proteolytic protection assay. All different inactivation methods resulted in a loss of HCV infectivity by targeting different parts of the virus particle. Alcohols such as ethanol and 2-propanol did not affect the viral RNA genome integrity but disrupted the viral envelope membrane in a capsid protection assay. Heat and UV treatment of HCV particles resulted in direct damage of the viral genome since transfection of viral particle-associated RNA into permissive cells did not initiate RNA replication. In addition, heat incubation at 80°C disrupted the HCV envelope, rendering the viral capsid susceptible to proteolytic digest. This study demonstrated the molecular processes of viral inactivation of an enveloped virus and should facilitate the development of effective disinfection strategies in infection control not only against HCV but also against other enveloped viruses. PMID:25527548

  2. INACTIVATION OF HEPATITIS A VIRUS AND MODEL VIRUSES IN WATER BY FREE CHLORINE AND MONOCHLORAMINE

    EPA Science Inventory

    The kinetics and extent of inactivation of hepatitis A virus (HAV) as well as three other viruses, coxsackievirus B5 (CB5) and coliphages MS2 and X174, by 0.5 mg/l free chlorine, pH 6-10, and 10 mg/1 monochloramine, pH8, in 0.01 M phosphate buffer were determined. These results i...

  3. Detection of SENV Virus in Healthy, Hepatitis B- and Hepatitis C-Infected Individuals in Yazd Province, Iran

    PubMed Central

    Hosseini, Sayedeh Azimeh; Bouzari, Majid

    2016-01-01

    Background: SEN virus (SENV) is the latest virus proposed as a cause of unknown hepatitis cases. Among nine detected genotypes of the virus, genotypes D and H are more frequent in hepatitis cases of unknown origin. The aim of this study was to determine the frequency of SENV-D and SENV-H genotypes in the sera of healthy individuals and hepatitis B and C patients. Methods: Totally, 200 serum samples from healthy individuals as well as 50 hepatitis B and 50 hepatitis C patients were collected. Anti-HCV (hepatitis C virus), anti-human immunodeficiency virus, hepatitis B surface antigen and anti-HBV (hepatitis B virus) core antigen were detected, and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured. Viral DNA was subjected to nested PCR. Fisher's exact and unpaired ANOVA tests were used for statistical analyses. Results: SENV was detected in 90%, 66%, and 46% of the healthy individuals HBV and HCV-positive individuals, respectively. The frequency of SENV and its two genotypes were significantly lower in hepatitis B and hepatitis C patients (P<0.01). Also, the frequency of SENV-H was higher than SENV-D in all studied groups. In SENV-positive HBV patients, the level of ALT and AST enzymes were significantly less than SENV-negative patients (P<0.05). It was the same for SENV-H-negative and -positive cases. Conclusions: The levels of liver enzymes were significantly lower in HBV patients co-infected with SENV compared to HBV patients (P<0.05), indicating a positive impact of the virus in liver pathology by decreasing liver damage and thus decreasing the liver enzymes. PMID:26948255

  4. The yin and yang of hepatitis C: synthesis and decay of hepatitis C virus RNA.

    PubMed

    Li, You; Yamane, Daisuke; Masaki, Takahiro; Lemon, Stanley M

    2015-09-01

    Hepatitis C virus (HCV) is an unusual RNA virus that has a striking capacity to persist for the remaining life of the host in the majority of infected individuals. In order to persist, HCV must balance viral RNA synthesis and decay in infected cells. In this Review, we focus on interactions between the positive-sense RNA genome of HCV and the host RNA-binding proteins and microRNAs, and describe how these interactions influence the competing processes of viral RNA synthesis and decay to achieve stable, long-term persistence of the viral genome. Furthermore, we discuss how these processes affect hepatitis C pathogenesis and therapeutic strategies against HCV. PMID:26256788

  5. Evolution of hepatitis B virus liver disease after hepatic replacement. Practical and theoretical considerations.

    PubMed Central

    Demetris, A. J.; Todo, S.; Van Thiel, D. H.; Fung, J. J.; Iwaki, Y.; Sysyn, G.; Ming, W.; Trager, J.; Starzl, T. E.

    1990-01-01

    The morphologic evolution of hepatitis B virus (HBV) liver disease in 45 hepatic allograft recipients who were HBV surface-antigen positive (HBs-Ag+) at the time of liver replacement and who survived for more than 60 days was studied by routine histologic and immunocytochemical analysis of serial pathology specimens. The findings in these patients were compared to a control group of 30 individuals who were immune to the HBV (anti-HBs antibody positive), but required hepatic replacement for other reasons. Eight of the forty-five (18%) HBsAg-positive patients have no serologic evidence of HBV reinfection after transplantation. All 37 remaining patients are reinfected; 21 (47%) developed chronic active hepatitis and/or cirrhosis, 3 (7%) developed submassive necrosis, and 6 (14%) developed chronic lobular hepatitis. One patient lost her graft to chronic rejection, despite reinfection with the B virus. Four other patients (9%) developed a chronic carrier state. No long-term follow-up biopsies were available in the remaining two patients. The histologic features associated with dysfunction related to recurrent HBV infection evolved from an acute to chronic phase and were similar to hepatitis B seen in nonallografted livers. Furthermore HBV-related lesions could be separated from rejection using routine histology alone. The only exception to this conclusion was the occurrence of a peculiar HBV-related lesion in two recipients, described herein. Immunohistochemical analysis demonstrated the presence of viral antigens in almost all cases. Hepatic inflammation also was commonly present during HBV disease and consisted mostly of accessory cells and T lymphocytes. Analysis of the effect of major histocompatibility complex matching revealed no clear association between the number of class I or II matches or mismatches and the development, or pattern, of active hepatitis in the allograft. Peculiar pathologic alterations in several of the biopsies and failed allografts after HBV

  6. Multiplex qPCR for serodetection and serotyping of hepatitis viruses: A brief review

    PubMed Central

    Irshad, Mohammad; Gupta, Priyanka; Mankotia, Dhananjay Singh; Ansari, Mohammad Ahmad

    2016-01-01

    The present review describes the current status of multiplex quantitative real time polymerase chain reaction (qPCR) assays developed and used globally for detection and subtyping of hepatitis viruses in body fluids. Several studies have reported the use of multiplex qPCR for the detection of hepatitis viruses, including hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and hepatitis E virus (HEV). In addition, multiplex qPCR has also been developed for genotyping HBV, HCV, and HEV subtypes. Although a single step multiplex qPCR assay for all six hepatitis viruses, i.e., A to G viruses, is not yet reported, it may be available in the near future as the technologies continue to advance. All studies use a conserved region of the viral genome as the basis of amplification and hydrolysis probes as the preferred chemistries for improved detection. Based on a standard plot prepared using varying concentrations of template and the observed threshold cycle value, it is possible to determine the linear dynamic range and to calculate an exact copy number of virus in the specimen. Advantages of multiplex qPCR assay over singleplex or other molecular techniques in samples from patients with co-infection include fast results, low cost, and a single step investigation process. PMID:27239109

  7. Multiplex qPCR for serodetection and serotyping of hepatitis viruses: A brief review.

    PubMed

    Irshad, Mohammad; Gupta, Priyanka; Mankotia, Dhananjay Singh; Ansari, Mohammad Ahmad

    2016-05-28

    The present review describes the current status of multiplex quantitative real time polymerase chain reaction (qPCR) assays developed and used globally for detection and subtyping of hepatitis viruses in body fluids. Several studies have reported the use of multiplex qPCR for the detection of hepatitis viruses, including hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and hepatitis E virus (HEV). In addition, multiplex qPCR has also been developed for genotyping HBV, HCV, and HEV subtypes. Although a single step multiplex qPCR assay for all six hepatitis viruses, i.e., A to G viruses, is not yet reported, it may be available in the near future as the technologies continue to advance. All studies use a conserved region of the viral genome as the basis of amplification and hydrolysis probes as the preferred chemistries for improved detection. Based on a standard plot prepared using varying concentrations of template and the observed threshold cycle value, it is possible to determine the linear dynamic range and to calculate an exact copy number of virus in the specimen. Advantages of multiplex qPCR assay over singleplex or other molecular techniques in samples from patients with co-infection include fast results, low cost, and a single step investigation process. PMID:27239109

  8. Early predictive efficacy of core antigen on antiviral outcomes in genotype 1 hepatitis C virus infected patients.

    PubMed

    Feng, Bo; Yang, Rui-Feng; Zhang, Hai-Ying; Luo, Bi-Fen; Kong, Fan-Yun; Rao, Hui-Ying; Jin, Qian; Cong, Xu; Wei, Lai

    2015-01-01

    Response-guided therapy is of limited use in developing countries because hepatitis C virus RNA detection by sensitive molecular methods is time- and labor-consuming and expensive. We evaluated early predictive efficacy of serum hepatitis C virus core antigen kinetics on sustained virologic response in patients with genotype 1 hepatitis C virus during pegylated interferon plus ribavirin treatment. For 478 patients recruited, hepatitis C virus RNAs were detected at baseline, and at weeks 4, 12, 24, 48, and 72 using Cobas TaqMan. Architect hepatitis C virus core antigen was performed at baseline, and weeks 4 and 12. Predictive values of hepatitis C virus core antigen on sustained virologic response were compared to hepatitis C virus RNA. In the first 12 weeks after treatment initiation the dynamic patterns of serum hepatitis C virus core antigen and hepatitis C virus RNA levels were similar in sustained virologic response, relapse, and null response patients groups. Although areas under the receiver operating characteristics curves of hepatitis C virus core antigen were lower than those of hepatitis C virus RNA at the same time points, modeling analysis showed that undetectable hepatitis C virus core antigen (rapid virological response based on hepatitis C virus core antigen) had similar positive predictive value on sustained virologic response to hepatitis C virus RNA at week 4 (90.4% vs 93.3%), and hepatitis C virus core antigen decrease greater than 1log10IU/mL (early virological response based on hepatitis C virus core antigen) had similar negative predictive value to hepatitis C virus RNA at week 12 (94.1% vs 95.2%). Analysis on the validation group demonstrated a positive predictive value of 97.5% in rapid virological response based on hepatitis C virus core antigen and a negative predictive value of 100% in early virological response based on hepatitis C virus core antigen. In conclusion, hepatitis C virus core antigen is comparable to hepatitis C virus RNA in

  9. Optimal management of hepatitis B virus infection - EASL Special Conference.

    PubMed

    Lampertico, Pietro; Maini, Mala; Papatheodoridis, George

    2015-11-01

    There have been great strides in the management of chronic hepatitis B virus (HBV) infection, but considerable challenges remain. The European Association for the Study of the Liver (EASL) convened a special conference focusing on all clinical aspects of the management of this disease. Immigration patterns are having a huge effect on the incidence, prevalence and genotype predominance of HBV in many European countries. In recent years there has been significant progress in our understanding of the virology and immunopathology of HBV, particularly the identification of the entry receptor for HBV conferring its hepatotropism, sodium taurocholate co-transporting polypeptide, and a better understanding of the regulation of the covalently closed circular DNA form of HBV - the major barrier to cure. However, more fundamental scientific research is needed. Serum biomarkers and transient elastography offer equivalent performance in the grading of disease stage and progression and monitoring of treatment. Occult HBV infection is often overlooked, but has many important implications for e.g., immuno-suppression, liver transplantation and the progression and severity of liver diseases from other causes. Hepatitis B e antigen positive immunotolerant patients, who are a significant source of horizontal and vertical transmission, are at risk for developing active chronic hepatitis B, but current treatment options are ineffective. Pegylated interferon therapy, given for a finite duration, offers sustained off-treatment responses in a minority of patients. Nucleos(t)ide analogues suppress the virus, improve liver histological lesions, reverse cirrhosis in the majority of cases, and improve survival, but 'cure' cannot be achieved. There is also a pressing need for novel HBV/hepatitis D virus co-infection therapies. Novel therapeutic strategies, e.g. immunomodulation, RNA interference and viral entry inhibition have demonstrated promising early results. PMID:26150256

  10. Molecular basis of interferon resistance in hepatitis C virus.

    PubMed

    Perales, Celia; Beach, Nathan M; Sheldon, Julie; Domingo, Esteban

    2014-10-01

    Resistance to interferon (IFN) in hepatitis C virus (HCV) differs from resistance to standard, directly-acting antiviral (DAA) agents in that the virus confronts a multicomponent antiviral state evoked by IFN. This renders unlikely the repeated selection of the same specific mutations that confer an IFN-resistance phenotype. Comparison of amino acid sequences of viral proteins in HCV that replicates in the presence of IFN in vivo or in cell culture (with entire virus or subgenomic replicons) reveals very few common candidate IFN resistance substitutions. Multiple host and viral factors contribute to divergent responses to IFN. The environmental heterogeneity in which exogenous IFN is expected to exert its selective effect may increase as a result of incorporation of new DAAs in therapy. PMID:24968186

  11. The pathogenesis of H3N8 canine influenza virus in chickens, turkeys and ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Canine influenza virus (CIV) of the H3N8 subtype has emerged in dog populations throughout the U.S. where is has become endemic in kennels and animal shelters in some regions. It has not previously been determined whether the canine adapted virus can be transmitted to domestic poultry, which are su...

  12. Susceptibility of wood ducks to H5N1 highly pathogenic avian influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Since 2002, H5N1 highly pathogenic avian influenza (HPAI) viruses have caused mortality in numerous species of wild birds; this is atypical for avian influenza virus (AIV) infections in wild birds, especially for species in the Order Anseriformes. Although these infections document the susceptibili...

  13. Links between human LINE-1 retrotransposons and hepatitis virus-related hepatocellular carcinoma

    NASA Astrophysics Data System (ADS)

    Honda, Tomoyuki

    2016-05-01

    Hepatocellular carcinoma (HCC) accounts for approximately 80% of liver cancers, the third most frequent cause of cancer mortality. The most prevalent risk factors for HCC are infections by hepatitis B or hepatitis C virus. Findings suggest that hepatitis virus-related HCC might be a cancer in which LINE-1 retrotransposons, often termed L1, activity plays a potential role. Firstly, hepatitis viruses can suppress host defense factors that also control L1 mobilization. Secondly, many recent studies also have indicated that hypomethylation of L1 affects the prognosis of HCC patients. Thirdly, endogenous L1 retrotransposition was demonstrated to activate oncogenic pathways in HCC. Fourthly, several L1 chimeric transcripts with host or viral genes are found in hepatitis virus-related HCC. Such lines of evidence suggest a linkage between L1 retrotransposons and hepatitis virus-related HCC. Here, I briefly summarize current understandings of the association between hepatitis virus-related HCC and L1. Then, I discuss potential mechanisms of how hepatitis viruses drive the development of HCC via L1 retrotransposons. An increased understanding of the contribution of L1 to hepatitis virus-related HCC may provide unique insights related to the development of novel therapeutics for this disease.

  14. Links between Human LINE-1 Retrotransposons and Hepatitis Virus-Related Hepatocellular Carcinoma

    PubMed Central

    Honda, Tomoyuki

    2016-01-01

    Hepatocellular carcinoma (HCC) accounts for approximately 80% of liver cancers, the third most frequent cause of cancer mortality. The most prevalent risk factors for HCC are infections by hepatitis B or hepatitis C virus. Findings suggest that hepatitis virus-related HCC might be a cancer in which LINE-1 retrotransposon, often termed L1, activity plays a potential role. Firstly, hepatitis viruses can suppress host defense factors that also control L1 mobilization. Secondly, many recent studies also have indicated that hypomethylation of L1 affects the prognosis of HCC patients. Thirdly, endogenous L1 retrotransposition was demonstrated to activate oncogenic pathways in HCC. Fourthly, several L1 chimeric transcripts with host or viral genes are found in hepatitis virus-related HCC. Such lines of evidence suggest a linkage between L1 retrotransposons and hepatitis virus-related HCC. Here, I briefly summarize current understandings of the association between hepatitis virus-related HCC and L1. Then, I discuss potential mechanisms of how hepatitis viruses drive the development of HCC via L1 retrotransposons. An increased understanding of the contribution of L1 to hepatitis virus-related HCC may provide unique insights related to the development of novel therapeutics for this disease. PMID:27242996

  15. Duck viral enteritis in domestic muscovy ducks in Pennsylvania

    USGS Publications Warehouse

    Davison, S.; Converse, K.A.; Hamir, A.N.; Eckroade, R.J.

    1993-01-01

    Duck viral enteritis (DVE) outbreaks occurred at two different locations in Pennsylvania in 1991 and 1992. In the first outbreak, four ducks died out of a group of 30 domestic ducks; in the second outbreak, 65 ducks died out of a group of 114 domestic ducks, and 15 domestic geese died as well. A variety of species of ducks were present on both premises, but only muscovy ducks (Cairina moschata) died from the disease. On necropsy, gross lesions included hepatomegaly with petechial hemorrhages, petechial hemorrhages in the abdominal fat, petechial hemorrhages on the epicardial surface of the heart, and multifocal to coalescing areas of fibrinonecrotic material over the mucosal surface of the trachea, esophagus, intestine, and cloaca. Histologically, the liver had random multifocal areas of necrosis and eosinophilic intranuclear inclusion bodies in hepatocytes. DVE virus was isolated and identified using muscovy duck embryo fibroblast inoculation and virus neutralization. /// En dos sitios diferentes se presentaron brotes de enteritis viral de los patos en el estados de Pensilvania en los a??os 1991 y 1992. En el primer brote, cuatro de un lote de 30 patos murieron mientras que en el segundo brote murieron 65 patos de un lote de 114 patos y 15 gansos. En ambas localidades exist?-a una variedad de especies de patos, sin embargo, s??lamente los patos almizcleros (Cairina moschata) murieron. A la necropsia, las lesiones macrosc??picas incluyeron hepatomegalia con hemorragias petequiales, hemorragias petequiales en la grasa abdominal y en la superficie del epicardio, y ?!reas multifocales o coalescentes de material fibrinonecr??tico sobre la superficie de la mucosa de la tr?!quea, es??fago, intestino y cloaca. Histol??gicamente, el h?-gado mostraba ?!reas multifocales de necrosis y cuerpos de inclusi??n intranucleares eosinof?-licos en los hepatocitos. El virus de la enteritis viral de los patos fue aislado e identificado usando fibroblasto de embriones de pato almizclero

  16. Postoperative hepatitis B virus reactivation in hepatitis B virus-related hepatocellular carcinoma patients with hepatitis B virus DNA levels <500 copies/mL

    PubMed Central

    Xie, Zhi-Bo; Wang, Xiao-Bo; Fu, De-Liang; Zhong, Jian-Hong; Yang, Xia-Wei; Li, Le-Qun

    2016-01-01

    Background Patients with hepatocellular carcinoma have the risk of postoperative hepatitis B virus (HBV) reactivation (PHR). Antiviral therapy was given to patients with detectable HBV DNA levels but not to patients with undetectable HBV DNA levels. Methods In this retrospective study, 258 patients were enrolled (HBV DNA levels <500 copies/mL group, n=159, and HBV DNA levels >500 copies/mL group, n=99). Results A total of 50 patients (19.4%) had PHR. The following significant factors related to PHR were found: without antiviral therapy (hazard ratio [HR] =0.17, 95% confidence interval [CI] 0.031–0.911), hepatitis B e antigen positivity (HR =5.20, 95% CI 1.931–14.007), hepatitis B core antigen S1 positivity (HR =2.54, 95% CI 1.116–5.762), preoperative HBV DNA levels ≥500 copies/mL (HR =1.28, 95% CI 1.085–2.884), hepatic inflow occlusion (HR =3.60, 95% CI 1.402–9.277), moderate liver cirrhosis or more (HR =2.26, 95% CI 1.001–5.121), and blood transfusion (HR =2.89, 95% CI 0.836–10.041). Recurrence-free survival time was significantly shorter in patients with PHR (23.06±2.46 months) than in patients without PHR (29.30±1.27 months). Conclusion Antiviral therapy could efficiently decrease the incidence of PHR. Patients with HBV DNA levels <500 copies/mL still have the risk of PHR. PHR remained as a prognostic risk factor for hepatocellular carcinoma recurrence and recurrence-free survival. PMID:27524913

  17. Despotic Ducks

    ERIC Educational Resources Information Center

    Darling, Randi A.

    2008-01-01

    This field experiment is designed to test for despotic behavior in Mallards ("Anas platyrhynchos"), and to examine how ducks distribute themselves relative to their resources. Students present Mallards with food patches differing in profitability in order to examine whether ducks distribute themselves ideal freely or ideal despotically. Students…

  18. Design and evaluation of a polytope construct with multiple B and T epitopes against Tembusu virus infection in ducks.

    PubMed

    Han, Kaikai; Zhao, Dongmin; Liu, Yuzhuo; Huang, Xinmei; Yang, Jing; Liu, Qingtao; An, Fengjiao; Li, Yin

    2016-02-01

    Tembusu virus (TMUV) is a newly emerging pathogenic flavivirus that is causing massive economic loss in Chinese poultry industry; until now, there is no effective vaccine or drug for its prevention. Epitope-based vaccination is a promising approach to achieve protective immunity and to avoid immunopathology. In present study, based on in silico epitope selection, we optimized and proposed a polytope DNA vaccine (pVAX1-rTEM) consisting B-cell and T cell epitopes from the TMUV envelope (E) protein. The immunogenicity and protective efficacy of constructed polytope DNA vaccine was assessed by in vitro and in vivo experiments. In in vitro assays, the expressed pVAX1-rTEM showed reactivity with Tembusu positive serum. Its protective efficacy against TMUV infection was evaluated in ducks. The results showed that pVAX1-rTEM was highly immunogenic and could elicit high titer neutralizing antibodies and cell-mediated immune responses. These results indicate that pVAX1-rTEM may be a promising candidate vaccine for prevention of TMUV infection. PMID:26850557

  19. Clinical implications of hepatitis B virus mutations: recent advances.

    PubMed

    Lazarevic, Ivana

    2014-06-28

    Hepatitis B virus (HBV) infection is a major cause of acute and chronic hepatitis, and of its long-term complications. It is the most variable among DNA viruses, mostly because of its unique life cycle which includes the activity of error-prone enzyme, reverse transcriptase, and the very high virion production per day. In last two decades, numerous research studies have shown that the speed of disease progression, reliability of diagnostic methods and the success of antiviral therapy and immunization are all influenced by genetic variability of this virus. It was shown that mutations in specific regions of HBV genome could be responsible for unwanted clinical outcomes or evasion of detection by diagnostic tools, thus making the monitoring for these mutations a necessity in proper evaluation of patients. The success of the vaccination programs has now been challenged by the discovery of mutant viruses showing amino acid substitutions in hepatitis B surface antigen (HBsAg), which may lead to evasion of vaccine-induced immunity. However, the emergence of these mutations has not yet raised concern since it was shown that they develop slowly. Investigations of HBV genetic variability and clinical implications of specific mutations have resulted in significant advances over the past decade, particularly in regard to management of resistance to antiviral drugs. In the era of drugs with high genetic barrier for resistance, on-going monitoring for possible resistance is still essential since prolonged therapy is often necessary. Understanding the frequencies and clinical implications of viral mutations may contribute to improvement of diagnostic procedures, more proper planning of immunization programs and creating the most efficient therapeutic protocols. PMID:24976703

  20. Clinical implications of hepatitis B virus mutations: Recent advances

    PubMed Central

    Lazarevic, Ivana

    2014-01-01

    Hepatitis B virus (HBV) infection is a major cause of acute and chronic hepatitis, and of its long-term complications. It is the most variable among DNA viruses, mostly because of its unique life cycle which includes the activity of error-prone enzyme, reverse transcriptase, and the very high virion production per day. In last two decades, numerous research studies have shown that the speed of disease progression, reliability of diagnostic methods and the success of antiviral therapy and immunization are all influenced by genetic variability of this virus. It was shown that mutations in specific regions of HBV genome could be responsible for unwanted clinical outcomes or evasion of detection by diagnostic tools, thus making the monitoring for these mutations a necessity in proper evaluation of patients. The success of the vaccination programs has now been challenged by the discovery of mutant viruses showing amino acid substitutions in hepatitis B surface antigen (HBsAg), which may lead to evasion of vaccine-induced immunity. However, the emergence of these mutations has not yet raised concern since it was shown that they develop slowly. Investigations of HBV genetic variability and clinical implications of specific mutations have resulted in significant advances over the past decade, particularly in regard to management of resistance to antiviral drugs. In the era of drugs with high genetic barrier for resistance, on-going monitoring for possible resistance is still essential since prolonged therapy is often necessary. Understanding the frequencies and clinical implications of viral mutations may contribute to improvement of diagnostic procedures, more proper planning of immunization programs and creating the most efficient therapeutic protocols. PMID:24976703

  1. Hepatitis E Virus Genotype 3 in Colombia: Survey in Patients with Clinical Diagnosis of Viral Hepatitis

    PubMed Central

    Rendon, Julio; Hoyos, Maria Cristina; di Filippo, Diana; Cortes-Mancera, Fabian; Mantilla, Carolina; Velasquez, Maria Mercedes; Sepulveda, Maria Elsy; Restrepo, Juan Carlos; Jaramillo, Sergio; Arbelaez, Maria Patricia; Correa, Gonzalo; Navas, Maria-Cristina

    2016-01-01

    Background Hepatitis E virus is a major cause of outbreaks as well as sporadic hepatitis cases worldwide. The epidemiology of this enterically transmitted infection differs between developing and developed countries. The aims of this study were to describe HEV infection in Colombian patients and to characterize the genotype. Methods A prospective study was carried out on 40 patients aged over 15 with a clinical diagnosis of viral hepatitis, recruited from five primary health units in the city of Medellin, Colombia. Fecal samples obtained from the 40 consecutives cases were analyzed for HEV RNA using nested reverse transcription PCR for both ORF1 and ORF2-3. The amplicons were sequenced for phylogenetic analyses. Results Nine (22.5%) cases of HEV infection were identified in the study population. Three HEV strains obtained from patients were classified as genotype 3. No significant association was found between cases of Hepatitis E and the variables water drinking source, garbage collection system and contact with pigs. Conclusions This is the first prospective study of hepatitis E in Colombian patients. The circulation of the genotype 3 in this population is predictable considering the reports of the region and the identification of this genotype from pigs in the state of Antioquia, of which Medellin is the capital. Further studies are necessary to establish whether zoonotic transmission of HEV is important in Colombia. PMID:26886728

  2. Expression and characterization of the UL31 protein from duck enteritis virus

    PubMed Central

    Xie, Wei; Cheng, Anchun; Wang, Mingshu; Chang, Hua; Zhu, Dekang; Luo, Qihui; Jia, Renyong; Chen, Xiaoyue

    2009-01-01

    Background Previous studies indicate that the UL31 protein and its homology play similar roles in nuclear egress of all herpesviruses. However, there is no report on the UL31 gene product of DEV. In this study, we expressed and presented the basic properties of the DEV UL31 product. Results The entire ORF of the UL31 was cloned into pET 32a (+) prokaryotic expression vector. Escherichia coli BL21(DE3) competent cells were transformed with the construct followed by the induction of protein expression by the addition of IPTG. Band corresponding to the predicted sizes (55 kDa) was produced on the SDS-PAGE. Over expressed 6×His-UL31 fusion protein was purified by nickel affinity chromatography. The DEV UL31 gene product has been identified by using a rabbit polyclonal antiserum raised against the purified protein. A protein of approximate 35 kDa that reacted with the antiserum was detected in immunoblots of DEV-infected cellular lysates, suggesting that the 35 kDa protein was the primary translation product of the UL31 gene. RT-PCR analyses revealed that the UL31 gene was transcribed most abundantly during the late phase of replication. Subsequently, Immunofluorescence analysis revealed that the protein was widespread speckled structures in the nuclei of infected cells. Western blotting of purified virion preparations showed that UL31 was a component of intracellular virions but was absent from mature extracellular virions. Finally, an Immunofluorescence assay was established to study the distribution of the UL31 antigen in tissues of artificially DEV infected ducks. The results showed that the UL31 antigen was primarily located in the cells of digestive organs and immunological organs. Conclusion In this work, we present the basic properties of the DEV UL31 product. The results indicate that DEV UL31 shares many similarities with its HSV or PRV homolog UL31 and suggest that functional cross-complementation is possible between members of the Alphaherpesvirus subfamily

  3. Genetic characterization of influenza A virus subtypes H1N3 and H1N9 isolated from free-grazing ducks in Thailand.

    PubMed

    Chaiyawong, Supassama; Boonyapisitsopa, Supanat; Jairak, Waleemas; Nonthabenjawan, Nutthawan; Tangwangvivat, Ratanaporn; Bunpapong, Napawan; Amonsin, Alongkorn

    2016-10-01

    Influenza A virus (IAV) subtype H1 has been reported to infect birds, pigs and humans. In this study, we characterized IAVs subtype H1N3 and H1N9 isolated from free-grazing ducks in Thailand. Phylogenetic analysis showed that Thai IAV-H1 isolates cluster with avian Eurasian-lineage but not pandemic H1N1 viruses. Analysis of the viruses indicated low-pathogenic avian influenza (LPAI) characteristics. This study is the first report of avian H1N3 and H1N9 in Thailand. Although Thai IAV-H1 viruses do not pose a risk of a pandemic, routine surveillance and genetic monitoring of IAVs should be conducted. PMID:27383209

  4. Hepatitis B virus infection and metabolic syndrome: fact or fiction?

    PubMed

    Wang, Chia-Chi; Tseng, Tai-Chung; Kao, Jia-Horng

    2015-01-01

    Although hepatitis C virus infection is known to be linked with insulin resistance, dyslipidemia, and hepatic steatosis, the relationship between hepatitis B virus (HBV) infection and metabolic factors remains unclear. HBV infection is a health problem worldwide, especially in endemic regions such as Asia and Africa. It induces liver decompensation, cirrhosis, hepatocellualr carcinoma, and premature mortality. The prevalence of metabolic syndrome continues to increase in parallel with the epidemic of obesity, which is closely associated with the development of diabetes, cardiovascular disease, or even cancer. The systemic review shows that chronic HBV infection protects against instead of promotes fatty liver. The mechanism is possibly due to a lower frequency of dyslipidemia profile in patients with chronic HBV infection. The association of HBV with metabolic syndrome, insulin resistance, and the risk of arteriosclerosis is still inconclusive. In addition, obesity, diabetes, and metabolic syndrome may accelerate the progression of liver disease in patients with chronic HBV infection and synergistically induce cirrhosis or even hepatocellualr carcinoma development. PMID:25092429

  5. Therapeutic Targets for the Treatment of Hepatitis E Virus Infection

    PubMed Central

    Kenney, Scott P.; Meng, Xiang-Jin

    2016-01-01

    Introduction Hepatitis E virus (HEV) is one of the most common causes of acute viral hepatitis in the world with an estimated 20 million infections per year. Although the mortality rate is less than 1% among the general population, pregnant women can have a fatality rate of up to 30%. Additionally, chronic hepatitis E has increasingly become a significant clinical problem in immunocompromised individuals. Effective antivirals against HEV are needed. Areas covered This review article addresses the current state of knowledge of HEV infections with regard to animal and cell culture model systems that are important for antiviral discovery and testing, our current understanding of the molecular mechanisms of virus replication, our understanding of how each viral protein functions, and areas that can potentially be exploited as therapeutic targets. Expert opinion Lack of an efficient cell culture system for HEV propagation, the limited knowledge of HEV lifecycle, and the inherent self-limiting infection within the normal populace make the development of new therapeutic agents against HEV challenging. There are many promising therapeutic targets, and the tools for identifying and testing potential antivirals are rapidly evolving. The development of effective therapeutics against HEV in immunocompromised and pregnant patient populations is warranted. PMID:26073772

  6. Hepatitis C virus infection of cholangiocarcinoma cell lines.

    PubMed

    Fletcher, Nicola F; Humphreys, Elizabeth; Jennings, Elliott; Osburn, William; Lissauer, Samantha; Wilson, Garrick K; van IJzendoorn, Sven C D; Baumert, Thomas F; Balfe, Peter; Afford, Simon; McKeating, Jane A

    2015-06-01

    Hepatitis C virus (HCV) infects the liver and hepatocytes are the major cell type supporting viral replication. Hepatocytes and cholangiocytes derive from a common hepatic progenitor cell that proliferates during inflammatory conditions, raising the possibility that cholangiocytes may support HCV replication and contribute to the hepatic reservoir. We screened cholangiocytes along with a panel of cholangiocarcinoma-derived cell lines for their ability to support HCV entry and replication. While primary cholangiocytes were refractory to infection and lacked expression of several entry factors, two cholangiocarcinoma lines, CC-LP-1 and Sk-ChA-1, supported efficient HCV entry; furthermore, Sk-ChA-1 cells supported full virus replication. In vivo cholangiocarcinomas expressed all of the essential HCV entry factors; however, cholangiocytes adjacent to the tumour and in normal tissue showed a similar pattern of receptor expression to ex vivo isolated cholangiocytes, lacking SR-BI expression, explaining their inability to support infection. This study provides the first report that HCV can infect cholangiocarcinoma cells and suggests that these heterogeneous tumours may provide a reservoir for HCV replication in vivo. PMID:25701818

  7. Hepatitis C virus infection of cholangiocarcinoma cell lines

    PubMed Central

    Fletcher, Nicola F.; Humphreys, Elizabeth; Jennings, Elliott; Osburn, William; Lissauer, Samantha; Wilson, Garrick K.; van IJzendoorn, Sven C. D.; Baumert, Thomas F.; Balfe, Peter; Afford, Simon

    2015-01-01

    Hepatitis C virus (HCV) infects the liver and hepatocytes are the major cell type supporting viral replication. Hepatocytes and cholangiocytes derive from a common hepatic progenitor cell that proliferates during inflammatory conditions, raising the possibility that cholangiocytes may support HCV replication and contribute to the hepatic reservoir. We screened cholangiocytes along with a panel of cholangiocarcinoma-derived cell lines for their ability to support HCV entry and replication. While primary cholangiocytes were refractory to infection and lacked expression of several entry factors, two cholangiocarcinoma lines, CC-LP-1 and Sk-ChA-1, supported efficient HCV entry; furthermore, Sk-ChA-1 cells supported full virus replication. In vivo cholangiocarcinomas expressed all of the essential HCV entry factors; however, cholangiocytes adjacent to the tumour and in normal tissue showed a similar pattern of receptor expression to ex vivo isolated cholangiocytes, lacking SR-BI expression, explaining their inability to support infection. This study provides the first report that HCV can infect cholangiocarcinoma cells and suggests that these heterogeneous tumours may provide a reservoir for HCV replication in vivo. PMID:25701818

  8. Hepatitis B Virus Infection, MicroRNAs and Liver Disease

    PubMed Central

    Sarkar, Neelakshi; Chakravarty, Runu

    2015-01-01

    Hepatitis B virus (HBV) attacks the liver and can cause both acute as well as chronic liver diseases which might lead to liver cirrhosis and hepatocellular carcinoma. Regardless of the availability of a vaccine and numerous treatment options, HBV is a major cause of morbidity and mortality across the world. Recently, microRNAs (miRNAs) have emerged as important modulators of gene function. Studies on the role of miRNA in the regulation of hepatitis B virus gene expression have been the focus of modern antiviral research. miRNAs can regulate viral replication and pathogenesis in a number of different ways, which includefacilitation, direct or indirect inhibition, activation of immune response, epigenetic modulation, etc. Nevertheless, these mechanisms can appropriately be used with a diagnosticand/or therapeutic approach. The present review is an attempt to classify specific miRNAs that are reported to be associated with various aspects of hepatitis B biology, in order to precisely present the participation of individual miRNAs in multiple aspects relating to HBV. PMID:26247932

  9. Characterization of monoclonal antibodies against duck Tembusu virus E protein: an antigen-capture ELISA for the detection of Tembusu virus infection.

    PubMed

    Bai, Xiaofei; Shaozhou, Wulin; Zhang, Qingshan; Li, Chenxi; Qiu, Na; Meng, Runzhe; Liu, Ming; Zhang, Yun

    2015-03-01

    The E protein of flaviviruses is the primary antigen that induces protective immunity, but a monoclonal antibody (mAb) against the E protein of duck Tembusu virus (DTMUV) has never been characterized. Six hybridoma cell lines secreting DTMUV anti-E mAbs were prepared and designated 2A5, 1F3, 1G2, 1B11, 3B6, and 4F9, respectively. An immunofluorescence assay indicated that the mAbs could specifically bind to duck embryo fibroblast (DEF) cells infected with DTMUV and that the E protein was distributed in the cytoplasm of the infected cells. Immunoglobulin isotyping differentiated the mAbs as IgG1 (1G2, 1B11, 4F9, 1F3, and 2A5) and IgG2b (3B6). The mAbs were used to identify three epitopes, A (2A5, 1F3, and 1G2), B (1B11 and 4F9), and C (3B6) on the E protein on the basis of a competitive binding assay. By using mAbs 1F3 and 3B6, we developed an antigen-capture enzyme-linked immunosorbent assay (AC-ELISA) to detect E antigen from clinical samples. The AC-ELISA did not react with other known pathogens, indicating that the mAbs are specific for DTMUV. Compared to RT-PCR, the specificity and sensitivity of the AC-ELISA was 94.1 % and 98.0 %, respectively. This AC-ELISA thus represents a sensitive and rapid method for detecting DTMUV infection in birds. PMID:25588821

  10. Screening for Hepatitis B Virus and Hepatitis C Virus at a Community Fair: A Single-Center Experience

    PubMed Central

    Woo, Garmen A.; Hill, Mary A.; de Medina, Maria D.

    2013-01-01

    Despite recommendations for screening for hepatitis B virus (HBV) and hepatitis C virus (HCV), most individuals are still unaware of their infection status. The disparities in screening for HBV and HCV can be attributed to lack of awareness, language barriers, and difficulty in accessing healthcare. To address these issues, an exhibit booth was set up at an annual cultural festival to promote awareness about HBV and HCV and also provide free screening for a local Floridian community. Recruitment was conducted in various languages by physicians and nurses who specialize in hepatology. All materials associated with the screening process were sponsored by the Schiff Center for Liver Diseases, which is located at the University of Miami Miller School of Medicine in Florida. In the first year of the screening initiative, 173 of 11,000 fair attendees were screened for HBV. Twenty-nine (17%) of those screened tested positive for antibodies to hepatitis B core antigen (anti-HBc), and only 1 individual tested positive for chronic HBV, with positive hepatitis B surface antigen (HBsAg). Screening for HCV and an extended patient questionnaire were added to the screening program in the second year of the initiative. A total 231 of 9,000 fair attendees volunteered to be screened for both HBV and HCV. Twenty-nine (13%) of these people tested positive for anti-HBc, and 3 tested positive for HBsAg. Only 1 person tested positive for anti-HCV, but this individual had undetectable HCV RNA levels. Our single-center experience illustrates that, despite efforts to improve access to screening, only 2-3% of attendees at a cultural fair embraced the screening efforts. Other strategies will be required to enhance participation in screening programs for viral hepatitis. PMID:23943664

  11. Effects of dietary gossypol concentration on growth performance, blood profiles, and hepatic histopathology in meat ducks1

    PubMed Central

    Zeng, Q. F.; Yang, G. L.; Liu, G. N.; Wang, J. P.; Bai, S. P.; Ding, X. M.; Luo, Y. H.; Zhang, K. Y.

    2014-01-01

    The objective of this study was to determine the effects of gossypol from cottonseed meal (CSM) on growth performance, blood biochemical profiles, and liver histopathology of ducks. A total of 900 1-d-old ducks were randomly allocated to 5 treatments with 12 pens/treatment and 15 ducks/pen. The 5 experimental diets were formulated in such a way that 0% (a corn-soybean meal basal diet, diet 1), 25% (diet 2), 50% (diet 3), 75% (diet 4), and 100% (diet 5) of protein from soybean meal were replaced with that from CSM. All diets were formulated on a digestible amino acid basis. The experiment included 2 phases, the starter phase (1 to 3 wk) where the test diets contained graded levels of CSM and the growth phase (4 to 5 wk) where birds were fed a corn-soybean basal diet to examine the recovery of ducks after CSM withdrawal. Dietary CSM and gossypol linearly (P < 0.01) and quadratically (P < 0.01) decreased ADG and ADFI during d 1 to 14. The threshold of daily total gossypol (TG) and free gossypol (FG) intake based on ADG on d 1 to 7 and d 7 to 14 were 32.20 and 2.64 mg/d, and 92.12 and 9.62 mg/d, respectively. Serum alanine aminotransferase increased (P < 0.05) linearly with increasing level of gossypol in the diets (d 7), whereas aspartate aminotransferase increased (P < 0.05) linearly and quadratically (d 14). Serum albumin concentration decreased (P < 0.05) quadratically with increasing dietary CSM concentrations on d 21. The degree of damage to the liver increased markedly with increasing dietary CSM and gossypol content and the length of CSM and gossypol intake. On d 35, there was no difference on BW and blood profiles of ducks among all treatments. These results suggest that meat ducks’ dietary TG and FG concentration should be lower than 928.9 and 77.2 mg/kg, respectively, during d 1 to 21 of age and that a 2-wk withdrawal of diets containing gossypol should be considered. PMID:24902707

  12. Evaluation of two different swab transport systems in the detection of avian influenza virus excretion from infected Pekin ducks (Anas platyrhynchos).

    PubMed

    Roelandt, Sophie; Outtrim, Linzy; Browning, Clare; Alexander, Dennis J; Brown, Ian H; Irvine, Richard M

    2012-09-01

    The role of wild birds in the epidemiology and ecology of influenza A viruses has long been recognised (Alexander, 2007a). As a result of the emergence of a H5N1 highly pathogenic avian influenza (HPAI) virus and the apparent role of wild birds in its spread across Asia, Europe and Africa, avian influenza (AI) wild bird surveillance has been implemented in many countries including, since February 2006, a mandatory programme in the European Union (CEC, 2006a). In the present study the detection of virus excreted from Pekin ducks (Anas platyrhynchos) infected experimentally with A/mallard/England/2126/07 (H3N6) was investigated over a fourteen day period post-infection using cloacal and oropharyngeal swabs, with (wet) and without (dry) viral transport medium which were collected from each duck in alternating order. For influenza A virus matrix gene RNA detection, wet oropharyngeal swabs were significantly more sensitive than dry oropharyngeal on days 4-5 after infection. For cloacal samples, dry swabs were equivalent or superior to wet swabs throughout the study. Although differences in detection between dry and wet swabs were observed, the qualitative bird-level results were unaffected, meaning that the infection status of individual birds was correctly determined. PMID:22609802

  13. Multiplex biomarker analysis biosensor for detection of hepatitis B virus.

    PubMed

    Xu, Hua; Gu, Dayong; He, Jian'an; Shi, Lei; Yao, Jingyu; Liu, Chunxiao; Zhao, Chunzhong; Xu, Yunqing; Jiang, Shengyang; Long, Jun

    2015-01-01

    In this paper, we report the development of a protein microarray-based biosensor for the detection of the hepatitis B virus (HBV) serological markers using surface plasmon resonance (SPR Printing buffer, protein immobilization time and concentration of the capture protein were optimized systematically to determine the best performance of the biosensor. Under optimal conditions, five hepatitis B markers in 20 μL human serum can be simultaneously detected within 30 minutes, whereas other methods such as ELISA and PCR can detect only one marker within four hours. This platform has been validated by analysis of 35 patients known to have hepatitis B, with 85% agreement between the test platform and analysis by commercial enzyme-linked immunosorbent assay (ELISA) kits. The results demonstrate that the protein microarray with SPR displayed a sensitivity of 0.1 ng mL(-1) for HBsAg. In addition to high sensitivity, it also shows excellent specificity, reproducibility and stability. This integrated protein microarray technique combined with SPR is a promising candidate for hepatitis B diagnosis with high-throughput. PMID:26405988

  14. Renal disease in patients infected with hepatitis B virus.

    PubMed

    Jaryal, Ajay; Kumar, Vivek; Sharma, Vishal

    2015-01-01

    Infection with hepatitis B virus (HBV) can result in hepatic diseases which may include an asymptomatic non-replicative carrier state, immunotolerant phase characterized by high DNA levels without significant hepatic injury, immune-reactive phase characterized by occurrence of chronic hepatitis and fibrosis in the liver, or complications like cirrhosis or hepatocellular carcinoma. Extrahepatic manifestations may also accompany HBV infection. These may include serum sickness syndrome, polyarthralgia, polyarthritis, dermatologic manifestations like pitted keratolysis, urticaria, purpura, oral lichen planus or Gianotti-Crosti syndrome-a childhood papular eruption. Renal involvement may occur with HBV infection and usually involves glomerular or vascular injury. Various morphologic forms of renal injury have been reported with HBV infection, the commonest being membranous glomerulonephritis. The manifestations may include swelling over face and body, pedal edema, and urinary abnormalities. Evaluation may detect proteinuria, hematuria and reduction in estimated glomerular filtration rate (GFR). The management options include use of antiviral drugs targeting HBV infection with or without concomitant immunosuppressive medication. With availability of newer drugs like entecavir and tenofovir, these have become the first line agents as they have a high barrier to resistance. Sole use of immunosuppression is not recommended for lack of clear benefit and the possible risk of HBV reactivation or flare. PMID:27509699

  15. Shedding of Hepatitis C Virus in Semen of Human Immunodeficiency Virus-Infected Men

    PubMed Central

    Turner, Samuel S.; Gianella, Sara; Yip, Marcus J-S.; van Seggelen, Wouter O.; Gillies, Robert D.; Foster, Andrew L.; Barbati, Zachary R.; Smith, Davey M.; Fierer, Daniel S.

    2016-01-01

    Background. The epidemic of sexually transmitted hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) has been documented for over a decade. Despite this, there is no consensus as to the risk factors for sexual acquisition of HCV in these men. Methods. We obtained paired semen and blood samples at 2-week intervals from HIV-infected MSM with recent and chronic HCV infection and quantified HCV in semen. Results. Hepatitis C virus was quantified in 59 semen specimens from 33 men. Hepatitis C virus was shed in 16 (27%) of semen specimens from 11 (33%) of the men. Median HCV viral load (VL) in semen was 1.49 log10 IU/mL. Hepatitis C virus VL in blood was significantly higher at the time of HCV shedding in semen than when HCV shedding in semen was not detected (P = .002). Furthermore, there was a significant correlation between the HCV VL in blood and semen overall (rs = 0.41; P = .001), and in the subgroup with recent HCV infection (rs = 0.37; P = .02), but not in the subgroup with chronic HCV infection (rs = 0.34; P = .1). Conclusions. One third of HIV-infected MSM coinfected with HCV shed HCV into their semen. Based on the HCV VL in semen in this study, an average ejaculate would deliver up to 6630 IU of virus into the rectum of the receptive partner. Therefore, our data strongly support that condoms should be used during anal intercourse among MSM to prevent transmission of HCV. PMID:27186582

  16. Hepatitis E virus antibody prevalence in wildlife in Poland.

    PubMed

    Larska, M; Krzysiak, M K; Jabłoński, A; Kęsik, J; Bednarski, M; Rola, J

    2015-03-01

    Hepatitis E is an important public health problem mostly in developing but occasionally also in industrialized countries. Domestic and wildlife animals are considered reservoirs of the hepatitis E virus (HEV). Since no information on the prevalence of autochthonous HEV infections in human and animal in Poland is available, the aim of the study was to investigate the HEV seroprevalence of different wildlife species as potential virus reservoirs in the country. No HEV antibodies were found in any of the sera collected from the red deer (Cervus elaphus), European bison (Bison bonasus), roe deer (Capreolus capreolus), elk (Alces alces), fallow deer (Dama dama), sika deer (Cervus nippon), Tatra chamois (Rupicapra rupicapra tatrica) or brown bear (Ursus arctos). HEV-specific antibodies were detected in 44.4% (95% CI 38.3-50.7) serum samples originated only from wild boars. The percentage of seropositive wild boars differed significantly between the provinces and was positively correlated with the wild boar density and rurality of the area. This study showed that HEV circulates among wild boar population in Poland, and this species should be considered as an important reservoir of the virus. PMID:24655475

  17. Direct evidence for cytotoxicity associated with expression of hepatitis delta virus antigen.

    PubMed

    Cole, S M; Gowans, E J; Macnaughton, T B; Hall, P D; Burrell, C J

    1991-05-01

    It has been postulated that hepatocyte injury resulting from infection with hepatitis D virus may be caused by a direct virus cytotoxicity in contrast to immune-mediated injury associated with hepatitis B virus. We have transfected HeLa and HepG2 continuous cell lines with a recombinant plasmid containing the hepatitis D antigen gene under the inducible control of the human metallothionein promoter. The addition of zinc to the cell culture medium then led to the expression of hepatitis D antigen associated with, in the short term, a significant reduction in the rate of RNA but not DNA synthesis and, in the longer term, cell death. The necrotic cells had pyknotic nuclei and shrunken eosinophilic cytoplasm; these necrotic cells resembled the apoptotic bodies seen in hepatitis D virus-related hepatitis. The level of hepatitis D antigen in individual cells that produced these changes was similar to the level of hepatitis D antigen in hepatocytes from a chimpanzee with acute hepatitis D virus infection. We conclude that the expression of hepatitis D antigen resulted in significant cytotoxic changes in these cells, providing strong support for the view that hepatitis D antigen may be specifically cytotoxic to infected hepatocytes in vivo. PMID:1709411

  18. A Protocol for Analyzing Hepatitis C Virus Replication

    PubMed Central

    Arumugaswami, Vaithilingaraja

    2014-01-01

    Hepatitis C Virus (HCV) affects 3% of the world’s population and causes serious liver ailments including chronic hepatitis, cirrhosis, and hepatocellular carcinoma. HCV is an enveloped RNA virus belonging to the family Flaviviridae. Current treatment is not fully effective and causes adverse side effects. There is no HCV vaccine available. Thus, continued effort is required for developing a vaccine and better therapy. An HCV cell culture system is critical for studying various stages of HCV growth including viral entry, genome replication, packaging, and egress. In the current procedure presented, we used a wild-type intragenotype 2a chimeric virus, FNX-HCV, and a recombinant FNX-Rluc virus carrying a Renilla luciferase reporter gene to study the virus replication. A human hepatoma cell line (Huh-7 based) was used for transfection of in vitro transcribed HCV genomic RNAs. Cell-free culture supernatants, protein lysates and total RNA were harvested at various time points post-transfection to assess HCV growth. HCV genome replication status was evaluated by quantitative RT-PCR and visualizing the presence of HCV double-stranded RNA. The HCV protein expression was verified by Western blot and immunofluorescence assays using antibodies specific for HCV NS3 and NS5A proteins. HCV RNA transfected cells released infectious particles into culture supernatant and the viral titer was measured. Luciferase assays were utilized to assess the replication level and infectivity of reporter HCV. In conclusion, we present various virological assays for characterizing different stages of the HCV replication cycle. PMID:24998302

  19. Rapid and quantitative detection of hepatitis B virus

    PubMed Central

    Liu, Yue-Ping; Yao, Chun-Yan

    2015-01-01

    Despite availability of a universal vaccine, hepatitis B virus (HBV) infection has a huge impact on public health worldwide. Accurate and timely diagnosis of HBV infection is needed. Rapid developments have been made in the diagnostic and monitoring methods for HBV infection, including serological and molecular assays. In clinical practice, qualitative hepatitis B surface antigen (HBsAg) testing has long served as a diagnostic marker for individuals infected with HBV. More recently, HBsAg level has been used to predict treatment outcome when determined early during treatment or at baseline. However, identification of HBV DNA positive cases that do not have detectable HBsAg has encouraged the application of molecular tests. Hence, combination of quantitative detection of HBV DNA and HBsAg can be used to discriminate patients during the course of HBV infection and to monitor therapy. This article reviews the most commonly used quantitative methods for HBsAg and HBV DNA. PMID:26576084

  20. Morphine Enhances Hepatitis C Virus (HCV) Replicon Expression

    PubMed Central

    Li, Yuan; Zhang, Ting; Douglas, Steven D.; Lai, Jian-Ping; Xiao, Wei-Dong; Pleasure, David E.; Ho, Wen-Zhe

    2003-01-01

    Little information is available regarding whether substance abuse enhances hepatitis C virus (HCV) replication and promotes HCV disease progression. We investigated whether morphine alters HCV mRNA expression in HCV replicon-containing liver cells. Morphine significantly increased HCV mRNA expression, an effect which could be abolished by either of the opioid receptor antagonists, naltrexone or β-funaltrexamine. Investigation of the mechanism responsible for this enhancement of HCV replicon expression demonstrated that morphine activated NF-κB promoter and that caffeic acid phenethyl ester, a specific inhibitor of the activation of NF-κB, blocked morphine-activated HCV RNA expression. In addition, morphine compromised the anti-HCV effect of interferon alpha (IFN-α). Our in vitro data indicate that morphine may play an important role as a positive regulator of HCV replication in human hepatic cells and may compromise IFN-α therapy. PMID:12937158

  1. Hepatitis C Virus NS3 Inhibitors: Current and Future Perspectives

    PubMed Central

    Akimitsu, Nobuyoshi

    2013-01-01

    Currently, hepatitis C virus (HCV) infection is considered a serious health-care problem all over the world. A good number of direct-acting antivirals (DAAs) against HCV infection are in clinical progress including NS3-4A protease inhibitors, RNA-dependent RNA polymerase inhibitors, and NS5A inhibitors as well as host targeted inhibitors. Two NS3-4A protease inhibitors (telaprevir and boceprevir) have been recently approved for the treatment of hepatitis C in combination with standard of care (pegylated interferon plus ribavirin). The new therapy has significantly improved sustained virologic response (SVR); however, the adverse effects associated with this therapy are still the main concern. In addition to the emergence of viral resistance, other targets must be continually developed. One such underdeveloped target is the helicase portion of the HCV NS3 protein. This review article summarizes our current understanding of HCV treatment, particularly with those of NS3 inhibitors. PMID:24282816

  2. Hepatitis C Virus E2 Envelope Glycoprotein Core Structure

    SciTech Connect

    Kong, Leopold; Giang, Erick; Nieusma, Travis; Kadam, Rameshwar U.; Cogburn, Kristin E.; Hua, Yuanzi; Dai, Xiaoping; Stanfield, Robyn L.; Burton, Dennis R.; Ward, Andrew B.; Wilson, Ian A.; Law, Mansun

    2014-08-26

    Hepatitis C virus (HCV), a Hepacivirus, is a major cause of viral hepatitis, liver cirrhosis, and hepatocellular carcinoma. HCV envelope glycoproteins E1 and E2 mediate fusion and entry into host cells and are the primary targets of the humoral immune response. The crystal structure of the E2 core bound to broadly neutralizing antibody AR3C at 2.65 angstroms reveals a compact architecture composed of a central immunoglobulin-fold β sandwich flanked by two additional protein layers. The CD81 receptor binding site was identified by electron microscopy and site-directed mutagenesis and overlaps with the AR3C epitope. The x-ray and electron microscopy E2 structures differ markedly from predictions of an extended, three-domain, class II fusion protein fold and therefore provide valuable information for HCV drug and vaccine design.

  3. Advances and Challenges in Studying Hepatitis B Virus In Vitro

    PubMed Central

    Witt-Kehati, Dvora; Bitton Alaluf, Maya; Shlomai, Amir

    2016-01-01

    Hepatitis B virus (HBV) is a small DNA virus that infects the liver. Current anti-HBV drugs efficiently suppress viral replication but do not eradicate the virus due to the persistence of its episomal DNA. Efforts to develop reliable in vitro systems to model HBV infection, an imperative tool for studying HBV biology and its interactions with the host, have been hampered by major limitations at the level of the virus, the host and infection readouts. This review summarizes major milestones in the development of in vitro systems to study HBV. Recent advances in our understanding of HBV biology, such as the discovery of the bile-acid pump sodium-taurocholate cotransporting polypeptide (NTCP) as a receptor for HBV, enabled the establishment of NTCP expressing hepatoma cell lines permissive for HBV infection. Furthermore, advanced tissue engineering techniques facilitate now the establishment of HBV infection systems based on primary human hepatocytes that maintain their phenotype and permissiveness for infection over time. The ability to differentiate inducible pluripotent stem cells into hepatocyte-like cells opens the door for studying HBV in a more isogenic background, as well. Thus, the recent advances in in vitro models for HBV infection holds promise for a better understanding of virus-host interactions and for future development of more definitive anti-viral drugs. PMID:26784218

  4. 77 FR 30293 - Recommendations for the Identification of Hepatitis C Virus (HCV) Chronic Infection

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-22

    ... Hepatitis C Virus (HCV) Chronic Infection AGENCY: Centers for Disease Control and Prevention (CDC... . Follow the instructions for submitting comments. Mail: Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention,...

  5. Linkage to Care for Suburban Heroin Users with Hepatitis C Virus Infection, New Jersey, USA.

    PubMed

    Akyar, Eda; Seneca, Kathleen H; Akyar, Serra; Schofield, Neal; Schwartz, Mark P; Nahass, Ronald G

    2016-05-01

    We identified a 41.4% prevalence of hepatitis C virus, absence of HIV, and unexpectedly high frequency of hepatitis C virus genotype 3 among suburban New Jersey heroin users 17-35 years of age during 2014-2015. Despite 2 clinicians prepared to engage these users, few were successfully linked to care and treated. PMID:27089172

  6. Linkage to Care for Suburban Heroin Users with Hepatitis C Virus Infection, New Jersey, USA

    PubMed Central

    Seneca, Kathleen H.; Akyar, Serra; Schofield, Neal; Schwartz, Mark P.; Nahass, Ronald G.

    2016-01-01

    We identified a 41.4% prevalence of hepatitis C virus, absence of HIV, and unexpectedly high frequency of hepatitis C virus genotype 3 among suburban New Jersey heroin users 17–35 years of age during 2014–2015. Despite 2 clinicians prepared to engage these users, few were successfully linked to care and treated. PMID:27089172

  7. High prevalence and predominance of hepatitis delta virus genotype 1 infection in Cameroon.

    PubMed

    Foupouapouognigni, Yacouba; Noah, Dominique Noah; Sartre, Michèle Tagni; Njouom, Richard

    2011-03-01

    Antibodies to the hepatitis delta virus (HDV) were found in 17.6% of 233 hepatitis B virus surface antigen-positive subjects in Cameroon. Phylogenetic analyses showed the presence of HDV-1, HDV-5, HDV-6, and HDV-7 genotypes. These results enrich the limited data on HDV prevalence and molecular diversity in Cameroon. PMID:21209162

  8. High Prevalence and Predominance of Hepatitis Delta Virus Genotype 1 Infection in Cameroon▿

    PubMed Central

    Foupouapouognigni, Yacouba; Noah, Dominique Noah; Sartre, Michèle Tagni; Njouom, Richard

    2011-01-01

    Antibodies to the hepatitis delta virus (HDV) were found in 17.6% of 233 hepatitis B virus surface antigen-positive subjects in Cameroon. Phylogenetic analyses showed the presence of HDV-1, HDV-5, HDV-6, and HDV-7 genotypes. These results enrich the limited data on HDV prevalence and molecular diversity in Cameroon. PMID:21209162

  9. Large-Scale Production and Structural and Biophysical Characterizations of the Human Hepatitis B Virus Polymerase

    PubMed Central

    Vörös, Judit; Urbanek, Annika; Rautureau, Gilles Jean Philippe; O'Connor, Maggie; Fisher, Henry C.; Ashcroft, Alison E.

    2014-01-01

    ABSTRACT Hepatitis B virus (HBV) is a major human pathogen that causes serious liver disease and 600,000 deaths annually. Approved therapies for treating chronic HBV infections usually target the multifunctional viral polymerase (hPOL). Unfortunately, these therapies—broad-spectrum antivirals—are not general cures, have side effects, and cause viral resistance. While hPOL remains an attractive therapeutic target, it is notoriously difficult to express and purify in a soluble form at yields appropriate for structural studies. Thus, no empirical structural data exist for hPOL, and this impedes medicinal chemistry and rational lead discovery efforts targeting HBV. Here, we present an efficient strategy to overexpress recombinant hPOL domains in Escherichia coli, purifying them at high yield and solving their known aggregation tendencies. This allowed us to perform the first structural and biophysical characterizations of hPOL domains. Apo-hPOL domains adopt mainly α-helical structures with small amounts of β-sheet structures. Our recombinant material exhibited metal-dependent, reverse transcriptase activity in vitro, with metal binding modulating the hPOL structure. Calcomine orange 2RS, a small molecule that inhibits duck HBV POL activity, also inhibited the in vitro priming activity of recombinant hPOL. Our work paves the way for structural and biophysical characterizations of hPOL and should facilitate high-throughput lead discovery for HBV. IMPORTANCE The viral polymerase from human hepatitis B virus (hPOL) is a well-validated therapeutic target. However, recombinant hPOL has a well-deserved reputation for being extremely difficult to express in a soluble, active form in yields appropriate to the structural studies that usually play an important role in drug discovery programs. This has hindered the development of much-needed new antivirals for HBV. However, we have solved this problem and report here procedures for expressing recombinant hPOL domains in

  10. High-level hepatitis B virus replication in transgenic mice.

    PubMed Central

    Guidotti, L G; Matzke, B; Schaller, H; Chisari, F V

    1995-01-01

    Hepatitis B virus (HBV) transgenic mice whose hepatocytes replicate the virus at levels comparable to that in the infected livers of patients with chronic hepatitis have been produced, without any evidence of cytopathology. High-level viral gene expression was obtained in the liver and kidney tissues in three independent lineages. These animals were produced with a terminally redundant viral DNA construct (HBV 1.3) that starts just upstream of HBV enhancer I, extends completely around the circular viral genome, and ends just downstream of the unique polyadenylation site in HBV. In these animals, the viral mRNA is more abundant in centrilobular hepatocytes than elsewhere in the hepatic lobule. High-level viral DNA replication occurs inside viral nucleocapsid particles that preferentially form in the cytoplasm of these centrilobular hepatocytes, suggesting that an expression threshold must be reached for nucleocapsid assembly and viral replication to occur. Despite the restricted distribution of the viral replication machinery in centrilobular cytoplasmic nucleocapsids, nucleocapsid particles are detectable in the vast majority of hepatocyte nuclei throughout the hepatic lobule. The intranuclear nucleocapsid particles are empty, however, suggesting that viral nucleocapsid particle assembly occurs independently in the nucleus and the cytoplasm of the hepatocyte and implying that cytoplasmic nucleocapsid particles do not transport the viral genome across the nuclear membrane into the nucleus during the viral life cycle. This model creates the opportunity to examine the influence of viral and host factors on HBV pathogenesis and replication and to assess the antiviral potential of pharmacological agents and physiological processes, including the immune response. PMID:7666518

  11. 75 FR 55797 - Draft Guidance for Industry on Chronic Hepatitis C Virus Infection: Developing Direct-Acting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-14

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Chronic Hepatitis C Virus... availability of a draft guidance for industry entitled ``Chronic Hepatitis C Virus Infection: Developing Direct... specific steps in the hepatitis C virus (HCV) replication cycle. The guidance outlines the types...

  12. Characterization of hepatitis delta virus in sub-Saharan Africa.

    PubMed

    Andernach, Iris E; Leiss, Lukas V; Tarnagda, Zekiba S; Tahita, Marc C; Otegbayo, Jesse A; Forbi, Joseph C; Omilabu, Sunday; Gouandjika-Vasilache, Ionela; Komas, Narcisse P; Mbah, Okwen P; Muller, Claude P

    2014-05-01

    Hepatitis D virus (HDV) is a satellite of hepatitis B virus (HBV), and infection with this virus aggravates acute and chronic liver disease. While HBV seroprevalence is very high across sub-Saharan Africa, much less is known about HDV in the region. In this study, almost 2,300 blood serum samples from Burkina Faso (n=1,131), Nigeria (n=974), Chad (n=50), and the Central African Republic (n = 118) were screened for HBV and HDV. Among 743 HBsAg-positive serum samples, 74 were positive for HDV antibodies and/or HDV RNA, with considerable differences in prevalence, ranging from <2% (pregnant women from Burkina Faso) to 50% (liver patients from Central African Republic). HDV seems to be much more common in chronic liver disease patients in the Central African Republic (CAR) than in similar cohorts in Nigeria. In a large nested mother-child cohort in Burkina Faso, the prevalence of HDV antibodies was 10 times higher in the children than in their mothers, despite similar HBsAg prevalences, excluding vertical transmission as an important route of infection. The genotyping of 16 full-length and 8 partial HDV strains revealed clade 1 (17/24) in three of the four countries, while clades 5 (5/24) and 6 (2/24) were, at least in this study, confined to Central Nigeria. On the amino acid level, almost all our clade 1 strains exhibited a serine at position 202 in the hepatitis D antigen, supporting the hypothesis of an ancient African HDV-1 subgroup. Further studies are required to understand the public health significance of the highly varied HDV prevalences in different cohorts and countries in sub-Saharan Africa. PMID:24599979

  13. Characterization of Hepatitis Delta Virus in Sub-Saharan Africa

    PubMed Central

    Andernach, Iris E.; Leiss, Lukas V.; Tarnagda, Zekiba S.; Tahita, Marc C.; Otegbayo, Jesse A.; Forbi, Joseph C.; Omilabu, Sunday; Gouandjika-Vasilache, Ionela; Komas, Narcisse P.; Mbah, Okwen P.

    2014-01-01

    Hepatitis D virus (HDV) is a satellite of hepatitis B virus (HBV), and infection with this virus aggravates acute and chronic liver disease. While HBV seroprevalence is very high across sub-Saharan Africa, much less is known about HDV in the region. In this study, almost 2,300 blood serum samples from Burkina Faso (n = 1,131), Nigeria (n = 974), Chad (n = 50), and the Central African Republic (n = 118) were screened for HBV and HDV. Among 743 HBsAg-positive serum samples, 74 were positive for HDV antibodies and/or HDV RNA, with considerable differences in prevalence, ranging from <2% (pregnant women from Burkina Faso) to 50% (liver patients from Central African Republic). HDV seems to be much more common in chronic liver disease patients in the Central African Republic (CAR) than in similar cohorts in Nigeria. In a large nested mother-child cohort in Burkina Faso, the prevalence of HDV antibodies was 10 times higher in the children than in their mothers, despite similar HBsAg prevalences, excluding vertical transmission as an important route of infection. The genotyping of 16 full-length and 8 partial HDV strains revealed clade 1 (17/24) in three of the four countries, while clades 5 (5/24) and 6 (2/24) were, at least in this study, confined to Central Nigeria. On the amino acid level, almost all our clade 1 strains exhibited a serine at position 202 in the hepatitis D antigen, supporting the hypothesis of an ancient African HDV-1 subgroup. Further studies are required to understand the public health significance of the highly varied HDV prevalences in different cohorts and countries in sub-Saharan Africa. PMID:24599979

  14. Extra-hepatic manifestations associated with hepatitis E virus infection: a comprehensive review of the literature

    PubMed Central

    Bazerbachi, Fateh; Haffar, Samir; Garg, Sushil K; Lake, John R

    2016-01-01

    Background and aims: Hepatitis E virus (HEV) infection is a significant public health problem that afflicts almost 20 million individuals annually and causes acute liver injury in 3.5 million, with approximately 56 000 deaths. As with other viral hepatitides, extra-hepatic manifestations could represent an important aspect of this infection. The spectrum of these manifestations is still emerging. Acute pancreatitis and neurological, musculoskeletal, hematological, renal, and other immune-mediated manifestations have been described. The aim of this article is to comprehensively review the published literature of extra-hepatic manifestations associated with HEV infection. Data sources: We searched the PubMed database using the MeSH term “hepatitis E” and each of the extra-hepatic manifestations associated with HEV infection. No language or date restrictions were set in these searches. Searches retrieving articles with non-A, non-B hepatitis were excluded. Additional articles were identified through the reference lists of included articles. Results: Several extra-hepatic manifestations associated with HEV infection have been published. The temporal association between some extra-hepatic manifestations and HEV infection and the exclusion of other possible etiologies suggests that HEV infection could have caused some of them. According to the available data, HEV infection appears to be strongly associated with acute pancreatitis, neurological disorders (with primarily dominant peripheral nerve involvement, most commonly manifested as Guillain-Barré syndrome, followed by neuralgic amyotrophy), hematological diseases (hemolytic anemia due to glucose phosphate dehydrogenase deficiency, and severe thrombocytopenia), glomerulonephritis, and mixed cryoglobulinemia. More data are needed to clarify whether an association exists with musculoskeletal or other immune-mediated manifestations. Conclusions: HEV infection should be considered in patients with acute pancreatitis

  15. DEVELOPMENT OF MULTIPLEX RT-PCR FOR THE DETECTION OF REOVIRUS, HEPATITIS A VIRUS, POLIOVIRUS, NORWALK VIRUS AND ROTAVIRUS

    EPA Science Inventory

    Water sources are often found to be contaminated by enteric viruses. This is a public health concern as food and waterborne outbreaks caused by enteric viruses such as noroviruses, rotaviruses, hepatitis A virus (HAV) and enteroviruses are a common occurrence. All of these viru...

  16. Vaccination against hepatitis viruses in Poland.

    PubMed

    Slusarczyk, J

    2001-03-21

    At present, two etiologic varieties of viral hepatitis (VH) can be directly vaccine-preventable: VH type A and VH type B. In addition, VH type D can be prevented indirectly through vaccination against VH-B. The first commercially available vaccine against VH-B appeared in 1981 and was human plasma-derived. After several years, it has generally been replaced by a recombinant type of vaccines. The obvious benefits of vaccination against VH-B prompted its introduction into the national immunization program in Poland in 1989. At that time, vaccination was offered free of charge to high-risk groups: newborns of HBsAg-carrier mothers, health-care workers, students: at medical schools, nursing schools, medical technology schools, and caretakers at institutions for mentally retarded persons. However, similarly to the experiences of other countries, observations in Poland indicated that such a targeted strategy fails to induce major epidemiological changes. In 1989 and in 1993, the incidence of VH-B per 100000 was 40.3 and 34.6, respectively. In addition, during these years, the incidence of V-B per 100000 children aged 0-4 years was 20.0 and 38.4, respectively. It has been decided that vaccination against VH-B will be obligatory for all newborns beginning from 1993. Due to financial constraints, it has been introduced in three phases, and since 1996, all newborns in Poland have been vaccinated. Already in 1993, three additional risk groups have been offered vaccination: patients with chronic diseases, patients awaiting planned surgery, and persons coming into close contact with acute VH-B or chronically HBV-infected individuals. In 1999, the incidence of VH-B per 100000 was 9.1/100000, and it may be assumed that vaccination helped to decrease the incidence of VH-B in Poland. The country experience with vaccination against VH-A is still limited. At present, it is recommended for children and adolescents and people dealing with food distribution, as well as for several other

  17. GB Virus C/Hepatitis G Virus (GBV-C/HGV): still looking for a disease

    PubMed Central

    Sathar, M A; Soni, P N; York, D

    2000-01-01

    GB Virus C and Hepatitis G Virus (GBV-C/HGV) are positive, single-stranded flaviviruses. GBV-C and HGV are independent isolates of the same virus. Transmission via the blood-borne route is the commonest mode, although vertical and sexual transmission is well documented. GBV-C/HGV is distributed globally; its prevalence in the general population is 10 fold higher in African countries than in non-African countries. High prevalences of GBV-C/HGV have been found in subjects with frequent parenteral exposure and in groups at high risk of exposure to blood and blood products. The clinical significance of human infection with GBV-C/HGV is currently unclear. The virus can establish both acute and chronic infection and appears to be sensitive to interferon. Only some 12–15% of chronic Non-A, B, C hepatitis cases are infected with GBV-C/HGV. A direct association with liver pathology is still lacking and it is not yet clear as to whether GBV-C/HGV is indeed a hepatotropic virus. Current evidence suggests that the spectrum of association of GBV-C/HGV infection with extrahepatic diseases ranges from haematalogical diseases, aplastic anaemia, human immunodeficiency virus (HIV)-positive idiopathic thrombocytopenia and thalassemia, through to common variable immune deficiency and cryoglobunemia. PMID:11168678

  18. Similar hepatitis C virus RNA kinetics in HIV/hepatitis C virus monoinfected genotype 2 or 3 matched controls during hepatitis C virus combination therapy.

    PubMed

    Karlström, Olle; Sönnerborg, Anders; Weiland, Ola

    2008-04-23

    We prospectively studied early hepatitis C virus kinetics and sustained virological response rates in HIV/HCV coinfected (n = 13) and HCV monoinfected matched controls (n = 26) with HCV genotype 2/3 treated with pegylated interferon (peg-IFN) alpha-2a 135 microg/week plus ribavirin 11 mg/kg daily during 24 weeks. No significant difference in HCV-RNA decay was seen at any time point during the initial 12 weeks of therapy. Sustained virological response was achieved in 9/13 (69%) versus 20/26 (77%) patients (intent-to-treat), respectively. The lower-than-standard peg-IFN dose offered high compliance and reasonable sustained virological response rates. PMID:18427210

  19. Hepatitis C virus relies on lipoproteins for its life cycle

    PubMed Central

    Grassi, Germana; Di Caprio, Giorgia; Fimia, Gian Maria; Ippolito, Giuseppe; Tripodi, Marco; Alonzi, Tonino

    2016-01-01

    Hepatitis C virus (HCV) infects over 150 million people worldwide. In most cases, HCV infection becomes chronic causing liver disease ranging from fibrosis to cirrhosis and hepatocellular carcinoma. Viral persistence and pathogenesis are due to the ability of HCV to deregulate specific host processes, mainly lipid metabolism and innate immunity. In particular, HCV exploits the lipoprotein machineries for almost all steps of its life cycle. The aim of this review is to summarize current knowledge concerning the interplay between HCV and lipoprotein metabolism. We discuss the role played by members of lipoproteins in HCV entry, replication and virion production. PMID:26877603

  20. Herpes simplex virus hepatitis 4 years after liver transplantation.

    PubMed

    Bissig, Karl-Dimiter; Zimmermann, Arthur; Bernasch, Dirke; Furrer, Hansjakob; Dufour, Jean-FranCois

    2003-01-01

    If not promptly recognized and treated, herpes simplex virus (HSV) hepatitis is associated with a high mortality. A patient transplanted for primary sclerosing cholangitis required, 4 years later, a colectomy for a steroid-resistant flare of ulcerative colitis. He subsequently developed fever, with genital and oral ulcerations. He was hospitalized for diabetic decompensation with massive elevation of serum aminotransferases. Examination revealed vesicles on the hands. Liver biopsy showed Cowdry type B inclusions. Therapy with acyclovir was immediately initiated and the patient recovered. This case illustrates the diagnostic importance of mucocutaneous lesions in the assessment of complications after liver transplantation. PMID:14614611

  1. The New Era of Hepatitis C Virus Therapy

    PubMed Central

    Al-Judaibi, Bandar

    2015-01-01

    The hepatitis C virus (HCV) has a significant medical and economic impact on societies around the world, and it has been estimated that 130-180 million people are infected with HCV. Therapies for HCV are currently undergoing a revolution. In recent years, several new treatments have been approved by the United States Food and Drug Administration, and many other treatments are in phase II or III clinical trials, including direct antiviral agents (DAAs). Due to recent major advances in the field of HCV therapy, a summary of findings on new HCV therapies are provided in this review article, including reports on new DAAs. PMID:26655128

  2. New perspectives in occult hepatitis C virus infection

    PubMed Central

    Carreño, Vicente; Bartolomé, Javier; Castillo, Inmaculada; Quiroga, Juan Antonio

    2012-01-01

    Occult hepatitis C virus (HCV) infection, defined as the presence of HCV RNA in liver and in peripheral blood mononuclear cells (PBMCs) in the absence of detectable viral RNA in serum by standard assays, can be found in anti-HCV positive patients with normal serum levels of liver enzymes and in anti-HCV negative patients with persistently elevated liver enzymes of unknown etiology. Occult HCV infection is distributed worldwide and all HCV genotypes seem to be involved in this infection. Occult hepatitis C has been found not only in anti-HCV positive subjects with normal values of liver enzymes or in chronic hepatitis of unknown origin but also in several groups at risk for HCV infection such as hemodialysis patients or family members of patients with occult HCV. This occult infection has been reported also in healthy populations without evidence of liver disease. Occult HCV infection seems to be less aggressive than chronic hepatitis C although patients affected by occult HCV may develop liver cirrhosis and even hepatocellular carcinoma. Thus, anti-HCV negative patients with occult HCV may benefit from antiviral therapy with pegylated-interferon plus ribavirin. The persistence of very low levels of HCV RNA in serum and in PBMCs, along with the maintenance of specific T-cell responses against HCV-antigens observed during a long-term follow-up of patients with occult hepatitis C, indicate that occult HCV is a persistent infection that is not spontaneously eradicated. This is an updated report on diagnosis, epidemiology and clinical implications of occult HCV with special emphasis on anti-HCV negative cases. PMID:22736911

  3. Chronic Hepatitis B Virus Infection: Disease Revisit and Management Recommendations.

    PubMed

    Yuen, Man-Fung; Ahn, Sang Hoon; Chen, Ding-Shinn; Chen, Pei-Jer; Dusheiko, Geoffrey M; Hou, Jin-Lin; Maddrey, Willis C; Mizokami, Masashi; Seto, Wai-Kay; Zoulim, Fabien; Lai, Ching-Lung

    2016-04-01

    Chronic hepatitis B virus (HBV) infection evolves from immune-tolerance phase, through immune clearance phase to a quiescent phase or reactivation as hepatitis B e antigen-negative hepatitis. Persistent infection may result in the development of cirrhosis and hepatocellular carcinoma (HCC). Host factors including gender, age, family history, HLA-DP, and viral factors including HBV DNA, genotypes, precore mutations, pre-S deletions, and hepatitis B surface antigen (HBsAg) level are associated with the development of these complications. Risk scores for the development of HCC have been derived. Patients with persistently elevated alanine aminotransferase levels (>30 for males; >19 U/L for females) and HBV DNA levels >2000 IU/mL should be treated. Patients with established cirrhosis with detectable HBV DNA should also be treated. The recommended first-line agents include pegylated interferon and 2 nucleos(t)ide analogs, entecavir and tenofovir. NAs require long-term treatment to maintain suppression of HBV DNA. They have been shown to decrease hepatic fibrosis, or reverse cirrhosis and to reduce the development of HCC. They have very low rates (0% to 1.2%) of resistance. HBsAg seroclearance, although the ideal endpoint, is only achievable in 10% to 12% of patients by multicenter trials usually studying relatively young patients. Patients on long-term treatment should be monitored for viral breakthrough that may be due to noncompliance or the development of resistance. Newer agents are under trials to enhance the rate of HBsAg seroclearance. However, even with the current NAs, long-term treatment of >6 years can markedly reduce the covalently closed circular DNA, the viral component responsible for initiation of viral replication. PMID:26840752

  4. Differing prospects for the future of using gene therapy to treat infections with hepatitis B virus and hepatitis C virus.

    PubMed

    Ely, Abdullah; Arbuthnot, Patrick

    2015-09-01

    Infections with hepatitis B and hepatitis C viruses (HBV and HCV) are major global causes of liver diseases, often become chronic, and may be complicated by cirrhosis and liver cancer. Although HBV and HCV share common clinical features, their molecular biology is very different. HBV is a DNA virus that replicates by a mechanism that involves reverse transcription. The replication intermediate comprising nuclear covalently closed circular DNA (cccDNA) is stable and is largely unaffected by currently licensed drugs. Disabling cccDNA using gene therapy, particularly through application of gene editing technology, shows promise. Advancing this strategy may lead to a cure of HBV infection. HCV differs from HBV in that it is an RNA virus that replicates exclusively in the cytoplasm of infected cells. RNAi-based gene silencing and inhibition of the function of microRNA-122 using antisense oligonucleotides have shown promise against HCV. However recent evidence indicates that HCV may be eliminated with a combination of drugs that achieves sustained inhibition of viral replication and provides a high barrier to viral resistance. The long term prospects of nucleic acid-based HCV treatment are likely to be influenced by the success and affordability of these directly acting small molecule drugs. Conversely, since HBV is not susceptible to elimination using a similar approach, developing gene therapy for HBV infection remains a priority. PMID:26463095

  5. Domestic ducks and H5N1 influenza epidemic, Thailand.

    PubMed

    Songserm, Thaweesak; Jam-on, Rungroj; Sae-Heng, Numdee; Meemak, Noppadol; Hulse-Post, Diane J; Sturm-Ramirez, Katharine M; Webster, Robert G

    2006-04-01

    In addition to causing 12 human deaths and 17 cases of human infection, the 2004 outbreak of H5N1 influenza virus in Thailand resulted in the death or slaughter of 60 million domestic fowl and the disruption of poultry production and trade. After domestic ducks were recognized as silent carriers of H5N1 influenza virus, government teams went into every village to cull flocks in which virus was detected; these team efforts markedly reduced H5N1 infection. Here we examine the pathobiology and epidemiology of H5N1 influenza virus in the 4 systems of duck raising used in Thailand in 2004. No influenza viruses were detected in ducks raised in "closed" houses with high biosecurity. However, H5N1 influenza virus was prevalent among ducks raised in "open" houses, free-ranging (grazing) ducks, and backyard ducks. PMID:16704804

  6. Experimental models for hepatitis C virus (HCV): new opportunities for combating hepatitis C.

    PubMed

    Trujillo-Murillo, Karina del Carmen; Garza-Rodríguez, María del Lourdes; Martínez-Rodríguez, Herminia Guadalupe; Barrera-Saldaña, Hugo Alberto; Bosques-Padilla, Francisco; Ramos-Jiménez, Javier; Rivas-Estilla, Ana María

    2004-01-01

    Infection with hepatitis C virus (HCV) is a global public health issue. More than 200 million people in the world are infected with HCV. Hepatitis C is considered one of the main causes of chronic hepatitis, cirrhosis, hepatocellular carcinoma and liver transplantation. The identification of the viral genome quickly allowed delineation of genomic organization, and the structure and biochemical characterization of the proteins of HCV. However, it has been difficult to study its life cycle, as well as the development of antiviral agents due to the lack of a system of permissible culture. Numerous attempts have been reported to establish an in vitro system for the study of HCV. Recently, a system of efficient culture was established that allows replication of subgenomic molecules of HCV in a cell line of human hepatoma. In this revision, after a brief description of the molecular biology, means of transmission and clinical characteristics of hepatitis C, some of the experimental models are described that have been developed to date, focusing mainly on the subgenomic replicon system and their use in the development of new antiviral treatments. PMID:15257247

  7. Role of occult hepatitis B virus infection in chronic hepatitis C.

    PubMed

    Coppola, Nicola; Onorato, Lorenzo; Pisaturo, Mariantonietta; Macera, Margherita; Sagnelli, Caterina; Martini, Salvatore; Sagnelli, Evangelista

    2015-11-14

    The development of sensitive assays to detect small amounts of hepatitis B virus (HBV) DNA has favored the identification of occult hepatitis B infection (OBI), a virological condition characterized by a low level of HBV replication with detectable levels of HBV DNA in liver tissue but an absence of detectable surface antigen of HBV (HBsAg) in serum. The gold standard to diagnose OBI is the detection of HBV DNA in the hepatocytes by highly sensitive and specific techniques, a diagnostic procedure requiring liver tissue to be tested and the use of non-standardized non-commercially available techniques. Consequently, in everyday clinical practice, the detection of anti-hepatitis B core antibody (anti-HBc) in serum of HBsAg-negative subjects is used as a surrogate marker to identify patients with OBI. In patients with chronic hepatitis C (CHC), OBI has been identified in nearly one-third of these cases. Considerable data suggest that OBI favors the increase of liver damage and the development of hepatocellular carcinoma (HCC) in patients with CHC. The data from other studies, however, indicate no influence of OBI on the natural history of CHC, particularly regarding the risk of developing HCC. PMID:26576082

  8. Hepatic expression of tumour necrosis factor-alpha in chronic hepatitis B virus infection.

    PubMed Central

    Hussain, M J; Lau, J Y; Williams, R; Vergani, D

    1994-01-01

    AIM--To determine the hepatic expression of tumour necrosis factor-alpha (TNF alpha) in patients with chronic hepatitis B virus (HBV) infection. METHODS--Frozen liver biopsy sections from 19 patients with chronic HBV infection were studied, 12 of whom were HBeAg positive and 10 serum HBV DNA positive. Hepatic expression of TNF alpha was determined using immunohistochemistry. RESULTS--Only infiltrating mononuclear cells showed immunoreactive staining for TNF alpha (median 2, range 0-3; n = 19) which appeared as diffuse positive staining material in the cytoplasm. Patients with active liver disease, assessed histologically and biochemically, had a higher level of expression, both in the number of TNF alpha positive cells and the proportion of TNF alpha positive infiltrating mononuclear cells. There was no correlation between the expression of TNF alpha and serological parameters of viral infection (HBeAg and HBV DNA status and HBV DNA concentrations). CONCLUSION--Hepatic expression of TNF alpha is increased in chronic HBV infection and is related to the activity of liver disease and not to the level of HBV replication. Images PMID:7876386

  9. Serum Ferritin as a Predictor of Host Response to Hepatitis B Virus Infection

    NASA Astrophysics Data System (ADS)

    Lustbader, Edward D.; Hann, Hie-Won L.; Blumberg, Baruch S.

    1983-04-01

    With hemodialysis patients, a high serum ferritin before there was serological evidence of hepatitis B virus infection increased the likelihood that the infection would be persistent. This finding suggested that hepatitis B virus is likely to infect and actively replicate in liver cells with the propensity for increased ferritin synthesis. The virus itself could stimulate the synthesis of ferritin in a cyclic positive feedback mechanism that increases intracellular ferritin concentration and, eventually, intracellular iron. Transformed liver cells have low iron content, do not replicate hepatitis B virus, and require iron for growth. Infected, nonmalignant liver cells could supply iron to the transformed cells and nourish their expansion.

  10. p53-Mediated Cellular Response to DNA Damage in Cells with Replicative Hepatitis B Virus

    NASA Astrophysics Data System (ADS)

    Puisieux, Alain; Ji, Jingwei; Guillot, Celine; Legros, Yann; Soussi, Thierry; Isselbacher, Kurt; Ozturk, Mehmet

    1995-02-01

    Wild-type p53 acts as a tumor suppressor gene by protecting cells from deleterious effects of genotoxic agents through the induction of a G_1/S arrest or apoptosis as a response to DNA damage. Transforming proteins of several oncogenic DNA viruses inactivate tumor suppressor activity of p53 by blocking this cellular response. To test whether hepatitis B virus displays a similar effect, we studied the p53-mediated cellular response to DNA damage in 2215 hepatoma cells with replicative hepatitis B virus. We demonstrate that hepatitis B virus replication does not interfere with known cellular functions of p53 protein.

  11. Discovery, Optimization, and Characterization of Novel Chlorcyclizine Derivatives for the Treatment of Hepatitis C Virus Infection

    PubMed Central

    2015-01-01

    Recently, we reported that chlorcyclizine (CCZ, Rac-2), an over-the-counter antihistamine piperazine drug, possesses in vitro and in vivo activity against hepatitis C virus. Here, we describe structure–activity relationship (SAR) efforts that resulted in the optimization of novel chlorcyclizine derivatives as anti-HCV agents. Several compounds exhibited EC50 values below 10 nM against HCV infection, cytotoxicity selectivity indices above 2000, and showed improved in vivo pharmacokinetic properties. The optimized molecules can serve as lead preclinical candidates for the treatment of hepatitis C virus infection and as probes to study hepatitis C virus pathogenesis and host–virus interaction. PMID:26599718

  12. Hepatitis C Virus. Strategies to Evade Antiviral Responses

    PubMed Central

    Gokhale, Nandan S.; Vazquez, Christine; Horner, Stacy M.

    2015-01-01

    Summary Hepatitis C virus (HCV) causes chronic liver disease and poses a major clinical and economic burden worldwide. HCV is an RNA virus that is sensed as non-self in the infected liver by host pattern recognition receptors, triggering downstream signaling to interferons (IFNs). The type III IFNs play an important role in immunity to HCV, and human genetic variation in their gene loci is associated with differential HCV infection outcomes. HCV evades host antiviral innate immune responses to mediate a persistent infection in the liver. This review focuses on anti-HCV innate immune sensing, innate signaling and effectors, and the processes and proteins used by HCV to evade and regulate host innate immunity. PMID:25983854

  13. Phage display creates innovative applications to combat hepatitis B virus

    PubMed Central

    Tan, Wen Siang; Ho, Kok Lian

    2014-01-01

    Hepatitis B virus (HBV) has killed countless lives in human history. The invention of HBV vaccines in the 20th century has reduced significantly the rate of the viral infection. However, currently there is no effective treatment for chronic HBV carriers. Newly emerging vaccine escape mutants and drug resistant strains have complicated the viral eradication program. The entire world is now facing a new threat of HBV and human immunodeficiency virus co-infection. Could phage display provide solutions to these life-threatening problems? This article reviews critically and comprehensively the innovative and potential applications of phage display in the development of vaccines, therapeutic agents, diagnostic reagents, as well as gene and drug delivery systems to combat HBV. The application of phage display in epitope mapping of HBV antigens is also discussed in detail. Although this review mainly focuses on HBV, the innovative applications of phage display could also be extended to other infectious diseases. PMID:25206271

  14. Hepatitis B virus induces hypoxia-inducible factor-2α expression through hepatitis B virus X protein.

    PubMed

    Hu, Jian-Li; Liu, Li-Ping; Yang, Sheng-Li; Fang, Xiefan; Wen, Lu; Ren, Quan-Guang; Yu, Chao

    2016-03-01

    A growing number of studies suggest that the hepatitis B virus X protein (HBx) enhances the protein stability of the hypoxia-inducible factor-1α (HIF-1α). However, the relationship between hepatitis B virus (HBV), HBx and hypoxia-inducible factor-2α (HIF-2α) has not yet been fully elucidated. Immunohistochemical analysis was employed to detect the expression of HIF-2α in normal liver, HBV-related chronic hepatitis, and HBV-related and non-HBV-related hepatocellular carcinoma (HCC) tissues. Quantitative real‑time PCR (qPCR) and western blotting were used to investigate the impact of HBV and HBx on the expression of HIF‑2α. Immunoprecipitation and immunofluorescence were applied to explore the underlying mechanisms. The HIF‑2α expression was found to be higher in HBV‑related chronic hepatitis tissues than in normal liver tissues. Furthermore, it was higher in HBV‑related HCC tissues and HBV‑integrated HepG2 cells than in the corresponding non‑HBV‑related HCC tissues and HepG2 cells. Both HBV and HBx enhanced the protein stability of HIF‑2α. HBx‑mediated upregulation of HIF‑2α resulted mainly from an inhibition of the degradation of HIF‑2α due to the binding of HBx to the von Hippel‑Lindau protein (pVHL). In addition, HBx upregulated the expression of HIF‑2α by activating the NF‑κB signaling pathway. Thus, the present study identified that HBV induces the HIF‑2α expression through its encoded protein HBx. This upregulates the HIF-2α expression by binding to the pVHL activating the NF-κB signaling pathway. PMID:26647960

  15. Empirical fitness models for hepatitis C virus immunogen design

    NASA Astrophysics Data System (ADS)

    Hart, Gregory R.; Ferguson, Andrew L.

    2015-12-01

    Hepatitis C virus (HCV) afflicts 170 million people worldwide, 2%-3% of the global population, and kills 350 000 each year. Prophylactic vaccination offers the most realistic and cost effective hope of controlling this epidemic in the developing world where expensive drug therapies are not available. Despite 20 years of research, the high mutability of the virus and lack of knowledge of what constitutes effective immune responses have impeded development of an effective vaccine. Coupling data mining of sequence databases with spin glass models from statistical physics, we have developed a computational approach to translate clinical sequence databases into empirical fitness landscapes quantifying the replicative capacity of the virus as a function of its amino acid sequence. These landscapes explicitly connect viral genotype to phenotypic fitness, and reveal vulnerable immunological targets within the viral proteome that can be exploited to rationally design vaccine immunogens. We have recovered the empirical fitness landscape for the HCV RNA-dependent RNA polymerase (protein NS5B) responsible for viral genome replication, and validated the predictions of our model by demonstrating excellent accord with experimental measurements and clinical observations. We have used our landscapes to perform exhaustive in silico screening of 16.8 million T-cell immunogen candidates to identify 86 optimal formulations. By reducing the search space of immunogen candidates by over five orders of magnitude, our approach can offer valuable savings in time, expense, and labor for experimental vaccine development and accelerate the search for a HCV vaccine. Abbreviations: HCV—hepatitis C virus, HLA—human leukocyte antigen, CTL—cytotoxic T lymphocyte, NS5B—nonstructural protein 5B, MSA—multiple sequence alignment, PEG-IFN—pegylated interferon.

  16. Evaluation of poultry diagnostic tests for avial influenza virus in duck origin samples

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Diagnostic test for the detection and identification of avian influenza virus (AIV) infection in chickens and turkeys have been well established and commercial test kits are available for some applications. However few, if any diagnostic tests have been validated or evaluated for use with specimens...

  17. Betaine Inhibits Hepatitis B Virus with an Advantage of Decreasing Resistance to Lamivudine and Interferon α.

    PubMed

    Zhang, Mengmeng; Wu, Xiaoying; Lai, Furao; Zhang, Xiaoyuan; Wu, Hui; Min, Tian

    2016-05-25

    Betaine (BET) is a native compound known for its ability to protect the liver from toxicants. However, few studies have examined the effects of BET on the most common cause of liver disease, hepatitis B virus (HBV). In this study, the anti-HBV activity of BET was assessed in vitro and in vivo using enzyme-linked immunosorbent assay, quantitative polymerase chain reaction, and Southern blotting. The resistance of HBV to lamivudine and interferon α is challenging in the clinical treatment of HBV. The effect of BET on resistance was also investigated. The results showed that the secretion of HBsAg (HBV surface antigen), HbeAg (HBV e antigen), and HBV DNA in HepG2.2.15 cells was significantly decreased by BET via suppression of GRP78 expression. In duck HBV (DHBV)-infected ducklings, 1.0 or 2.0 g/kg BET significantly reduced serum DHBV DNA, and DHBV DNA did not rebound after the 5 day withdrawal period. BET suppressed HBV DNA rebound produced by the resistance of HBV to lamivudine and decreased the resistance mutation (rtM204V/I) of HBV DNA. Supplementation of BET may improve the anti-HBV effect of interferon α by increasing the expression of antiviral dsRNA-dependent protein kinase induced by the JAK-STAT (JAK = Janus kinase; STAT = signal transducer and activator of transcription) signaling pathway. These results may provide useful information for the clinical application of BET and solution of HBV drug resistance in anti-HBV therapy. PMID:27144395

  18. Cross-Species Antiviral Activity of Goose Interferons against Duck Plague Virus Is Related to Its Positive Self-Feedback Regulation and Subsequent Interferon Stimulated Genes Induction

    PubMed Central

    Zhou, Hao; Chen, Shun; Zhou, Qin; Wei, Yunan; Wang, Mingshu; Jia, Renyong; Zhu, Dekang; Liu, Mafeng; Liu, Fei; Yang, Qiao; Wu, Ying; Sun, Kunfeng; Chen, Xiaoyue; Cheng, Anchun

    2016-01-01

    Interferons are a group of antiviral cytokines acting as the first line of defense in the antiviral immunity. Here, we describe the antiviral activity of goose type I interferon (IFNα) and type II interferon (IFNγ) against duck plague virus (DPV). Recombinant goose IFNα and IFNγ proteins of approximately 20 kDa and 18 kDa, respectively, were expressed. Following DPV-enhanced green fluorescent protein (EGFP) infection of duck embryo fibroblast cells (DEFs) with IFNα and IFNγ pre-treatment, the number of viral gene copies decreased more than 100-fold, with viral titers dropping approximately 100-fold. Compared to the control, DPV-EGFP cell positivity was decreased by goose IFNα and IFNγ at 36 hpi (3.89%; 0.79%) and 48 hpi (17.05%; 5.58%). In accordance with interferon-stimulated genes being the “workhorse” of IFN activity, the expression of duck myxovirus resistance (Mx) and oligoadenylate synthetases-like (OASL) was significantly upregulated (p < 0.001) by IFN treatment for 24 h. Interestingly, duck cells and goose cells showed a similar trend of increased ISG expression after goose IFNα and IFNγ pretreatment. Another interesting observation is that the positive feedback regulation of type I IFN and type II IFN by goose IFNα and IFNγ was confirmed in waterfowl for the first time. These results suggest that the antiviral activities of goose IFNα and IFNγ can likely be attributed to the potency with which downstream genes are induced by interferon. These findings will contribute to our understanding of the functional significance of the interferon antiviral system in aquatic birds and to the development of interferon-based prophylactic and therapeutic approaches against viral disease. PMID:27438848

  19. Cross-Species Antiviral Activity of Goose Interferons against Duck Plague Virus Is Related to Its Positive Self-Feedback Regulation and Subsequent Interferon Stimulated Genes Induction.

    PubMed

    Zhou, Hao; Chen, Shun; Zhou, Qin; Wei, Yunan; Wang, Mingshu; Jia, Renyong; Zhu, Dekang; Liu, Mafeng; Liu, Fei; Yang, Qiao; Wu, Ying; Sun, Kunfeng; Chen, Xiaoyue; Cheng, Anchun

    2016-01-01

    Interferons are a group of antiviral cytokines acting as the first line of defense in the antiviral immunity. Here, we describe the antiviral activity of goose type I interferon (IFNα) and type II interferon (IFNγ) against duck plague virus (DPV). Recombinant goose IFNα and IFNγ proteins of approximately 20 kDa and 18 kDa, respectively, were expressed. Following DPV-enhanced green fluorescent protein (EGFP) infection of duck embryo fibroblast cells (DEFs) with IFNα and IFNγ pre-treatment, the number of viral gene copies decreased more than 100-fold, with viral titers dropping approximately 100-fold. Compared to the control, DPV-EGFP cell positivity was decreased by goose IFNα and IFNγ at 36 hpi (3.89%; 0.79%) and 48 hpi (17.05%; 5.58%). In accordance with interferon-stimulated genes being the "workhorse" of IFN activity, the expression of duck myxovirus resistance (Mx) and oligoadenylate synthetases-like (OASL) was significantly upregulated (p < 0.001) by IFN treatment for 24 h. Interestingly, duck cells and goose cells showed a similar trend of increased ISG expression after goose IFNα and IFNγ pretreatment. Another interesting observation is that the positive feedback regulation of type I IFN and type II IFN by goose IFNα and IFNγ was confirmed in waterfowl for the first time. These results suggest that the antiviral activities of goose IFNα and IFNγ can likely be attributed to the potency with which downstream genes are induced by interferon. These findings will contribute to our understanding of the functional significance of the interferon antiviral system in aquatic birds and to the development of interferon-based prophylactic and therapeutic approaches against viral disease. PMID:27438848

  20. Hepatitis B virus e antigen induces activation of rat hepatic stellate cells

    SciTech Connect

    Zan, Yanlu; Zhang, Yuxia; Tien, Po

    2013-06-07

    Highlights: •HBeAg expression in HSCs induced production of ECM protein and liver fibrotic markers. •The activation and proliferation of HSCs were mediated by TGF-β. •HBeAg protein purified from cell medium directly activated HSCs. -- Abstract: Chronic hepatitis B virus infection is a major cause of hepatic fibrosis, leading to liver cirrhosis and hepatocellular carcinoma. Hepatitis B virus e antigen (HBeAg) is an accessory protein of HBV, not required for viral replication but important for natural infection in vivo. Hepatic stellate cells (HSCs) are the major producers of excessive extracellular matrix during liver fibrogenesis. Therefore, we examined the influence of HBeAg on HSCs. The rat HSC line HSC-T6 was transfected with HBeAg plasmids, and expression of α-smooth muscle actin, collagen I, transforming growth factor-β1 (TGF-β), and tissue inhibitors of metalloproteinase 1 (TIMP-1) was investigated by quantitative real-time PCR. The proliferation of HSCs was determined by MTS analysis. HBeAg transduction induced up-regulation of these fibrogenic genes and proliferation of HSCs. We found that HBeAg induced TGF-β secretion in HSCs, and the activation of HSCs was prevented by a neutralizing anti-TGF-β antibody. Depletion and addition of HBeAg protein in conditioned medium from HSC-T6 cells transduced with HBeAg indicated that HBeAg directly induced the activation and proliferation of rat primary HSCs. Taken together, HBeAg induces the activation and proliferation of HSCs, mainly mediated by TGF-β, and HBeAg protein purified from cell medium can directly activate HSCs.

  1. Adaptive immune response during hepatitis C virus infection

    PubMed Central

    Larrubia, Juan Ramón; Moreno-Cubero, Elia; Lokhande, Megha Uttam; García-Garzón, Silvia; Lázaro, Alicia; Miquel, Joaquín; Perna, Cristian; Sanz-de-Villalobos, Eduardo

    2014-01-01

    Hepatitis C virus (HCV) infection affects about 170 million people worldwide and it is a major cause of liver cirrhosis and hepatocellular carcinoma. HCV is a hepatotropic non-cytopathic virus able to persist in a great percentage of infected hosts due to its ability to escape from the immune control. Liver damage and disease progression during HCV infection are driven by both viral and host factors. Specifically, adaptive immune response carries out an essential task in controlling non-cytopathic viruses because of its ability to recognize infected cells and to destroy them by cytopathic mechanisms and to eliminate the virus by non-cytolytic machinery. HCV is able to impair this response by several means such as developing escape mutations in neutralizing antibodies and in T cell receptor viral epitope recognition sites and inducing HCV-specific cytotoxic T cell anergy and deletion. To impair HCV-specific T cell reactivity, HCV affects effector T cell regulation by modulating T helper and Treg response and by impairing the balance between positive and negative co-stimulatory molecules and between pro- and anti-apoptotic proteins. In this review, the role of adaptive immune response in controlling HCV infection and the HCV mechanisms to evade this response are reviewed. PMID:24707125

  2. A perspective on modelling hepatitis C virus infection.

    PubMed

    Guedj, J; Rong, L; Dahari, H; Perelson, A S

    2010-12-01

    By mathematically describing early hepatitis C virus (HCV) RNA decay after initiation of interferon (IFN)-based antiviral therapy, crucial parameters of the in vivo viral kinetics have been estimated, such as the rate of production and clearance of free virus, and the rate of loss of infected cells. Furthermore, by suggesting mechanisms of action for IFN and ribavirin mathematical modelling has provided a means for evaluating and optimizing treatment strategies. Here, we review recent modelling developments for understanding complex viral kinetics patterns, such as triphasic HCV RNA declines and viral rebounds observed in patients treated with pegylated interferon and ribavirin. Moreover, we discuss new modelling approaches developed to interpret the viral kinetics observed in clinical trials with direct-acting antiviral agents, which induce a rapid decline of wild-type virus but also engender a higher risk for emergence of drug-resistant variants. Lastly, as in vitro systems have allowed a better characterization of the virus lifecycle, we discuss new modelling approaches that combine the intracellular and the extracellular viral dynamics. PMID:20723038

  3. Innate immune targets of hepatitis B virus infection

    PubMed Central

    Zou, Zhi-Qiang; Wang, Li; Wang, Kai; Yu, Ji-Guang

    2016-01-01

    Approximately 400 million people are chronically infected with hepatitis B virus (HBV) globally despite the widespread immunization of HBV vaccine and the development of antiviral therapies. The immunopathogenesis of HBV infection is initiated and driven by complexed interactions between the host immune system and the virus. Host immune responses to viral particles and proteins are regarded as the main determinants of viral clearance or persistent infection and hepatocyte injury. Innate immune system is the first defending line of host preventing from virus invasion. It is acknowledged that HBV has developed active tactics to escape innate immune recognition or actively interfere with innate immune signaling pathways and induce immunosuppression, which favor their replication. HBV reduces the expression of pattern-recognition receptors in the innate immune cells in humans. Also, HBV may interrupt different parts of antiviral signaling pathways, leading to the reduced production of antiviral cytokines such as interferons that contribute to HBV immunopathogenesis. A full comprehension of the mechanisms as to how HBV inactivates various elements of the innate immune response to initiate and maintain a persistent infection can be helpful in designing new immunotherapeutic methods for preventing and eradicating the virus. In this review, we aimed to summarize different branches the innate immune targeted by HBV infection. The review paper provides evidence that multiple components of immune responses should be activated in combination with antiviral therapy to disrupt the tolerance to HBV for eliminating HBV infection. PMID:27330680

  4. Innate immune targets of hepatitis B virus infection.

    PubMed

    Zou, Zhi-Qiang; Wang, Li; Wang, Kai; Yu, Ji-Guang

    2016-06-18

    Approximately 400 million people are chronically infected with hepatitis B virus (HBV) globally despite the widespread immunization of HBV vaccine and the development of antiviral therapies. The immunopathogenesis of HBV infection is initiated and driven by complexed interactions between the host immune system and the virus. Host immune responses to viral particles and proteins are regarded as the main determinants of viral clearance or persistent infection and hepatocyte injury. Innate immune system is the first defending line of host preventing from virus invasion. It is acknowledged that HBV has developed active tactics to escape innate immune recognition or actively interfere with innate immune signaling pathways and induce immunosuppression, which favor their replication. HBV reduces the expression of pattern-recognition receptors in the innate immune cells in humans. Also, HBV may interrupt different parts of antiviral signaling pathways, leading to the reduced production of antiviral cytokines such as interferons that contribute to HBV immunopathogenesis. A full comprehension of the mechanisms as to how HBV inactivates various elements of the innate immune response to initiate and maintain a persistent infection can be helpful in designing new immunotherapeutic methods for preventing and eradicating the virus. In this review, we aimed to summarize different branches the innate immune targeted by HBV infection. The review paper provides evidence that multiple components of immune responses should be activated in combination with antiviral therapy to disrupt the tolerance to HBV for eliminating HBV infection. PMID:27330680

  5. Delta agent (Hepatitis D)

    MedlinePlus

    Hepatitis D virus ... Hepatitis D virus (HDV) is found only in people who carry the hepatitis B virus. HDV may make liver ... B virus but who never had symptoms. Hepatitis D infects about 15 million people worldwide. It occurs ...

  6. Hepatitis C Virus Resistance to Carbohydrate-Binding Agents

    PubMed Central

    Izquierdo, Laure; Oliveira, Catarina; Fournier, Carole; Descamps, Véronique; Morel, Virginie; Dubuisson, Jean; Brochot, Etienne; Francois, Catherine; Castelain, Sandrine; Duverlie, Gilles; Helle, Francois

    2016-01-01

    Carbohydrate binding agents (CBAs), including natural lectins, are more and more considered as broad-spectrum antivirals. These molecules are able to directly inhibit many viruses such as Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV), Dengue Virus, Ebola Virus or Severe Acute Respiratory Syndrome Coronavirus through binding to envelope protein N-glycans. In the case of HIV, it has been shown that CBAs select for mutant viruses with N-glycosylation site deletions which are more sensitive to neutralizing antibodies. In this study we aimed at evaluating the HCV resistance to CBAs in vitro. HCV was cultivated in the presence of increasing Galanthus nivalis agglutinin (GNA), Cyanovirin-N, Concanavalin-A or Griffithsin concentrations, during more than eight weeks. At the end of lectin exposure, the genome of the isolated strains was sequenced and several potential resistance mutations in the E1E2 envelope glycoproteins were identified. The effect of these mutations on viral fitness as well as on sensitivity to inhibition by lectins, soluble CD81 or the 3/11 neutralizing antibody was assessed. Surprisingly, none of these mutations, alone or in combination, conferred resistance to CBAs. In contrast, we observed that some mutants were more sensitive to 3/11 or CD81-LEL inhibition. Additionally, several mutations were identified in the Core and the non-structural proteins. Thus, our results suggest that in contrast to HIV, HCV resistance to CBAs is not directly conferred by mutations in the envelope protein genes but could occur through an indirect mechanism involving mutations in other viral proteins. Further investigations are needed to completely elucidate the underlying mechanisms. PMID:26871442

  7. Pharmacokinetics of hepatitis C virus NS5A inhibitor JNJ-56914845 (GSK2336805) in subjects with hepatic impairment.

    PubMed

    Adkison, Kimberly K; Gan, Jianjun; Elko-Simms, Lucinda; Gardner, Stephen; Dumont, Etienne; Jones, Lori S; Saunders, Joanne; Marbury, Thomas; Smith, William; Berg, Jolene; Galloway, Christopher; Stump, Patrick J

    2015-09-01

    JNJ-56914845 (GSK2336805) is a hepatitis C virus nonstructural protein 5A inhibitor under development for the treatment of chronic hepatitis C (CHC) infection. This open-label, parallel-group, 2-part study evaluated the pharmacokinetics and safety of a single oral 60 mg dose of JNJ-56914845 in 4 cohorts: healthy, mild, moderate, and severe hepatic impairment (n = 8/cohort). Severity of hepatic impairment was categorized using Child-Pugh score, and the healthy subjects were matched for age, sex, body mass index, and smoking status to the moderate hepatic impairment cohort. JNJ-56914845 plasma AUC0-∞ was 26%, 52%, and 45% lower in subjects with mild, moderate, and severe hepatic impairment, respectively, relative to healthy subjects with no difference in half-life among the groups. The apparent oral clearance and volume of distribution were higher in subjects with hepatic impairment. The lower plasma concentrations were largely explained by decreased plasma protein binding in hepatically impaired subjects. One subject with severe hepatic impairment had 2 non-drug-related serious adverse events: an esophageal bleed requiring hospitalization, encephalopathy. Although hepatically impaired subjects have lower exposures than healthy matched controls, they had similar or slightly higher exposures than those observed in past studies of noncirrhotic, CHC patients, suggesting that no dose adjustments for hepatic impairment will be needed. PMID:25857714

  8. Committee Opinion No. 655: Hepatitis B, Hepatitis C, and Human Immunodeficiency Virus Infections in Obstetrician-Gynecologists.

    PubMed

    2016-02-01

    To prevent transmission of bloodborne pathogens, it is important that health care providers adhere to standard precautions, follow fundamental infection-control principles, and use appropriate procedural techniques. All obstetrician-gynecologists who provide clinical care should receive the hepatitis B virus vaccine series. The Society for Healthcare Epidemiology of America has established guidelines for the management of health care providers who are infected with hepatitis B virus, hepatitis C virus, or human immunodeficiency virus (HIV). The guidelines categorize representative obstetric and gynecologic procedures according to level of risk of bloodborne pathogen transmission and include recommendations for health care provider clinical activities, based on these categories and viral burden. It is important to note that when no restrictions are recommended, careful supervision should be carried out as highlighted. These recommendations provide a framework within which to consider such cases; however, each case should be independently considered in context by the expert review panel. PMID:26942390

  9. Committee Opinion No. 655 Summary: Hepatitis B, Hepatitis C, and Human Immunodeficiency Virus Infections in Obstetrician-Gynecologists.

    PubMed

    2016-02-01

    To prevent transmission of bloodborne pathogens, it is important that health care providers adhere to standard precautions, follow fundamental infection-control principles, and use appropriate procedural techniques. All obstetrician-gynecologists who provide clinical care should receive the hepatitis B virus vaccine series. The Society for Healthcare Epidemiology of America has established guidelines for the management of health care providers who are infected with hepatitis B virus, hepatitis C virus, or human immunodeficiency virus (HIV). The guidelines categorize representative obstetric and gynecologic procedures according to level of risk of bloodborne pathogen transmission and include recommendations for health care provider clinical activities, based on these categories and viral burden. It is important to note that when no restrictions are recommended, careful supervision should be carried out as highlighted. These recommendations provide a framework within which to consider such cases; however, each case should be independently considered in context by the expert review panel. PMID:26942383

  10. Seroepidemiology of hepatitis B virus infection and impact of vaccination

    PubMed Central

    Huang, Peng; Zhu, Li-Guo; Zhu, Ye-Fei; Yue, Ming; Su, Jing; Zhu, Feng-Cai; Yang, Hai-Tao; Zhang, Yun; Shen, Hong-Bing; Yu, Rong-Bin; Zhai, Xiang-Jun; Peng, Zhi-Hang

    2015-01-01

    AIM: To investigate hepatitis B virus (HBV) prevalence in the general population in China. METHODS: A total of 148931 individuals were investigated by multistage random sampling in Eastern China. Data were collected on demographics and hepatitis B vaccination history, and serum was tested for hepatitis B surface antigen (HBsAg) by ELISA. RESULTS: A total of 11469 participants (7.70%, 95%CI: 7.57%-7.84%) were positive for HBsAg. HBsAg prevalence was 0.77% among children < 5 years old but increased progressively from adolescents (1.40%-2.55%) to adults (5.69%-11.22%). A decrease in HBsAg prevalence was strongly associated with vaccination and familial history of HBV among both children and adult groups. Meanwhile, HBsAg risk in adults was associated with invasive testing and sharing needles. The HBV immunization rate among participants aged < 20 years was 93.30% (95%CI: 93.01%-93.58%). Significant difference in HBsAg prevalence appeared between vaccinated and unvaccinated participants (3.59% vs 10.22%). CONCLUSION: Although the national goal of HBsAg prevalence < 1% among children < 5 years old has been reached, immunization programs should be maintained to prevent resurgence. PMID:26167084

  11. [Molecular mechanisms of hepatitis B virus-associated hepatocellular carcinoma].

    PubMed

    Park, Neung Hwa; Chung, Young Hwa

    2007-09-01

    Hepatocellular carcinoma (HCC) is one of the most common malignant diseases in the world. The hepatitis B virus (HBV) replicates non-cytopathically in hepatocytes, and most of the liver injury associated with this infection reflects the immune response. Epidemiological studies have clearly demonstrated that a chronic HBV infection is a major etiological factor in the development of HCC. The pathogenesis of HBV-associated HCC has been studied extensively, and the molecular changes during the malignant transformation have been identified. The main carcinogenic mechanism of HBV-associated HCC is related to the long term-inflammatory changes caused by a chronic hepatitis B infection, which might involve the integration of the HBV. Integration of the HBV DNA into the host genome occurs at the early steps of clonal tumorous expansion. The hepatitis B x protein (HBx) is a multifunctional regulatory protein that communicates directly or indirectly with a variety of host targets, and mediates many opposing cellular functions, including its function in cell cycle regulation, transcriptional regulation, signaling, encoding of the cytoskeleton and cell adhesion molecules, as well as oncogenes and tumor suppressor genes. Continued study of the mechanisms of hepatocarcinogenesis will refine our current understanding of the molecular and cellular basis for neoplastic transformations in the liver. This review summarizes the current knowledge of the mechanisms involved in HBV-associated hepatocarcinogenesis. PMID:17898549

  12. Synthetic peptides for the immunodiagnosis of hepatitis A virus infection.

    PubMed

    Gauna, A; Losada, S; Lorenzo, M; Bermúdez, H; Toledo, M; Pérez, H; Chacón, E; Noya, O

    2015-12-01

    VP1, VP2 and VP3 molecules of hepatitis A virus are exposed capsid proteins that have shown to be antigenic and are used for diagnosis in recombinant-antigen commercial kits. In this study, we developed a sequence analysis in order to predict diagnostic peptide epitopes, followed by their spot synthesis on functionalized cellulose paper (Pepscan). This paper with synthetic peptides was tested against a sera pool of hepatitis A patients. Two peptide sequences, that have shown an antigenic recognition, were selected for greater scale synthesis on resin. A dimeric form of one of these peptides (IMT-1996), located in the C-Terminus region of protein VP1, was antigenic with a recognition frequency of 87-100% of anti-IgG antibodies and 100% of anti-IgM antibodies employing the immunological assays MABA and ELISA. We propose peptide IMT-1996, with less than twenty residues, as a cheaper alternative for prevalence studies and diagnosis of hepatitis A infection. PMID:26321053

  13. Host Immune Status and Response to Hepatitis E Virus Infection

    PubMed Central

    Krain, Lisa J.; Nelson, Kenrad E.

    2014-01-01

    SUMMARY Hepatitis E virus (HEV), identified over 30 years ago, remains a serious threat to life, health, and productivity in developing countries where access to clean water is limited. Recognition that HEV also circulates as a zoonotic and food-borne pathogen in developed countries is more recent. Even without treatment, most cases of HEV-related acute viral hepatitis (with or without jaundice) resolve within 1 to 2 months. However, HEV sometimes leads to acute liver failure, chronic infection, or extrahepatic symptoms. The mechanisms of pathogenesis appear to be substantially immune mediated. This review covers the epidemiology of HEV infection worldwide, the humoral and cellular immune responses to HEV, and the persistence and protection of antibodies produced in response to both natural infection and vaccines. We focus on the contributions of altered immune states (associated with pregnancy, human immunodeficiency virus [HIV], and immunosuppressive agents used in cancer and transplant medicine) to the elevated risks of chronic infection (in immunosuppressed/immunocompromised patients) and acute liver failure and mortality (among pregnant women). We conclude by discussing outstanding questions about the immune response to HEV and interactions with hormones and comorbid conditions. These questions take on heightened importance now that a vaccine is available. PMID:24396140

  14. Tissue culture system for infection with human hepatitis delta virus.

    PubMed Central

    Sureau, C; Jacob, J R; Eichberg, J W; Lanford, R E

    1991-01-01

    An in vitro culture system was developed for assaying the infectivity of the human hepatitis delta virus (HDV). Hepatocytes were isolated from chimpanzee liver and grown in a serum-free medium. Cells were shown to be infectible by HDV and to remain susceptible to infection for at least 3 weeks in culture, as evidenced by the appearance of RNA species characteristic of HDV replication as early as 6 days postinfection. When repeated experiments were carried out on cells derived from an animal free of hepatitis B virus (HBV), HDV infection occurred in a consistent fashion but there was no indication of infection with the HBV that was present in the inoculum. Despite numerous attempts with different sources of HBV inocula free of HDV, there was no evidence that indicated susceptibility of these cells to HBV infection. This observation may indicate that HBV and HDV use different modes of entry into hepatocytes. When cells derived from an HBV-infected animal were exposed to HDV, synthesis and release of progeny HDV particles were obtained in addition to HBV replication and production of Dane particles. Although not infectible with HBV, primary cultures of chimpanzee hepatocytes are capable of supporting part of the life cycle of HBV and the entire life cycle of HDV. Images PMID:2041075

  15. Hepatitis E virus: foodborne, waterborne and zoonotic transmission.

    PubMed

    Yugo, Danielle M; Meng, Xiang-Jin

    2013-10-01

    Hepatitis E virus (HEV) is responsible for epidemics and endemics of acute hepatitis in humans, mainly through waterborne, foodborne, and zoonotic transmission routes. HEV is a single-stranded, positive-sense RNA virus classified in the family Hepeviridae and encompasses four known Genotypes (1-4), at least two new putative genotypes of mammalian HEV, and one floating genus of avian HEV. Genotypes 1 and 2 HEVs only affect humans, while Genotypes 3 and 4 are zoonotic and responsible for sporadic and autochthonous infections in both humans and several other animal species worldwide. HEV has an ever-expanding host range and has been identified in numerous animal species. Swine serve as a reservoir species for HEV transmission to humans; however, it is likely that other animal species may also act as reservoirs. HEV poses an important public health concern with cases of the disease definitively linked to handling of infected pigs, consumption of raw and undercooked animal meats, and animal manure contamination of drinking or irrigation water. Infectious HEV has been identified in numerous sources of concern including animal feces, sewage water, inadequately-treated water, contaminated shellfish and produce, as well as animal meats. Many aspects of HEV pathogenesis, replication, and immunological responses remain unknown, as HEV is an extremely understudied but important human pathogen. This article reviews the current understanding of HEV transmission routes with emphasis on food and environmental sources and the prevalence of HEV in animal species with zoonotic potential in humans. PMID:24071919

  16. Hepatitis E Virus: Foodborne, Waterborne and Zoonotic Transmission

    PubMed Central

    Yugo, Danielle M.; Meng, Xiang-Jin

    2013-01-01

    Hepatitis E virus (HEV) is responsible for epidemics and endemics of acute hepatitis in humans, mainly through waterborne, foodborne, and zoonotic transmission routes. HEV is a single-stranded, positive-sense RNA virus classified in the family Hepeviridae and encompasses four known Genotypes (1–4), at least two new putative genotypes of mammalian HEV, and one floating genus of avian HEV. Genotypes 1 and 2 HEVs only affect humans, while Genotypes 3 and 4 are zoonotic and responsible for sporadic and autochthonous infections in both humans and several other animal species worldwide. HEV has an ever-expanding host range and has been identified in numerous animal species. Swine serve as a reservoir species for HEV transmission to humans; however, it is likely that other animal species may also act as reservoirs. HEV poses an important public health concern with cases of the disease definitively linked to handling of infected pigs, consumption of raw and undercooked animal meats, and animal manure contamination of drinking or irrigation water. Infectious HEV has been identified in numerous sources of concern including animal feces, sewage water, inadequately-treated water, contaminated shellfish and produce, as well as animal meats. Many aspects of HEV pathogenesis, replication, and immunological responses remain unknown, as HEV is an extremely understudied but important human pathogen. This article reviews the current understanding of HEV transmission routes with emphasis on food and environmental sources and the prevalence of HEV in animal species with zoonotic potential in humans. PMID:24071919

  17. Hepatitis C Virus NS3/4A Protease Inhibitors.

    PubMed

    López-Labrador, Francesc-Xavier

    2008-11-01

    Chronic hepatitis C virus infection is a global problem worldwide due to the lack of an effective therapy (the current standard of care treatment is effective in about 40-50% of the cases), and the difficulties in developing a protective vaccine. Chronic infection progresses to end-stage liver disease and liver failure in a considerable number of infected individuals. Once liver function is compromised, the only reliable therapeutic intervention is liver transplantation. Unfortunately, re-infection of the graft is unavoidable, and a new chronic hepatitis is early established in transplant recipients, that can result in graft loss. Thus, there is an urgent need for new, specifically targeted therapies for the treatment of HCV chronic infection. Among the viral proteins, the NS3/4A protease and the NS5b RNA-dependent RNA-polymerase, essential for the virus life cycle, have concentrated the efforts in the development of new antivirals, and some promising ones have already entered clinical trials. In particular, inhibitors of the HCV NS3/4A protease are the most advanced in clinical development. This review summarizes the available data for the most important HCV NS3/4A protease inhibitors in development, the most recent patents of these type of compounds, the envisioned options for future HCV therapies, and the eventual impact of HCV genetic variability on resistance to new NS3/4A protease inhibitors. PMID:18991798

  18. Novel treatment options for hepatitis B virus infection.

    PubMed

    Kumar, Rakesh; Agrawal, Babita

    2004-02-01

    Chronic hepatitis B virus (HBV) infection affects between 350 and 400 million people globally. Interferon-alpha, lamivudine and adefovir (Hepsera) are approved for the treatment of chronic hepatitis B; however, the use of interferon-alpha is limited. Lamivudine and adefovir have excellent antiviral activity and oral bioavailability, although viral rebound after cessation of therapy and development of resistance after long-term therapy with lamivudine are major clinical limitations. Adefovir has proven to be effective against lamivudine-resistant strains in vitro and in vivo. The various steps of HBV replication provide opportunities for new antiviral drugs to interact with the virus. Recent developments, including new antivirals that interfere with viral DNA replication, hold promise for the future. Sustained reduction in viral load and improved treatment of chronic HBV infection could, in future, be achieved by the development of new drugs with different mechanisms of action and resistance profiles, and with combination therapy involving two or more nucleosides with or without immunomodulators. PMID:15043391

  19. Hepatitis B and D viruses replication interference: Influence of hepatitis B genotype

    PubMed Central

    Madejón, Antonio; Romero, Míriam; Hernández, Ángela; García-Sánchez, Araceli; Sánchez-Carrillo, Marta; Olveira, Antonio; García-Samaniego, Javier

    2016-01-01

    AIM: To study the hepatitis B virus (HBV) and hepatitis D virus (HDV) replication interferences in patients with chronic hepatitis delta infected with different HBV genotypes. METHODS: We conducted a transversal study including 68 chronic hepatitis delta (CHD) (37 HIV-positive) patients and a control group of 49 chronic hepatitis B (CHB) (22 HIV-positive) patients. In addition, a dynamic follow-up was performed in 16 CHD patients. In all the samples, the surface antigen of hepatitis B (HBsAg) serum titers were analyzed with the Monolisa HBsAg Ultra system (Bio-Rad), using as quantification standard a serial dilution curve of an international HBsAg standard. Serum HBV-DNA titers were analyzed using the Roche Cobas TaqMan (Roche, Barcelona, Spain), and the serum HDV-RNA using an in-house real-time qRT-PCR method, with TaqMan probes. HBV genotype was determined with the line immunoassay LiPA HBV genotyping system (Innogenetics, Ghent, Belgium). In those patients negative for LiPA assay, a nested PCR method of complete HBsAg coding region, followed by sequence analysis was applied. RESULTS: No differences in the HBV-DNA levels were found in CHB patients infected with different HBV genotypes. However, in CHD patients the HBV-DNA levels were lower in those infected with HBV-A than in those with HBV-D, both in HIV negative [median (IQR): 1.25 (1.00-1.35) vs 2.95 (2.07-3.93) log10 (copies/mL), P = 0.013] and HIV positive patients [2.63 (1.24-2.69) vs 7.25 (4.61-7.55) log10 (copies/mL), P < 0.001]. This was confirmed in the dynamic study of the HBV/HDV patients. These differences induce an under-estimation of HBV-A incidence in patients with CHD analyzed with LiPA assay. Finally, the HBsAg titers reflected no significant differences in CHD patients infected with HBV-A or D. CONCLUSION: Viral replication interference between HBV and HDV is HBV-genotype dependent, and more evident in patients infected with HBV-genotype A, than with HBV-D or E. PMID:27003993

  20. Immune response in domestic ducks following intradermal delivery of inactivated vaccine against H5N1 highly pathogenic avian influenza virus adjuvanted with oligodeoxynucleotides containing CpG motifs.

    PubMed

    Yuk, Seong-Su; Lee, Dong-Hun; Park, Jae-Keun; To, Eredene-Ochir; Kwon, Jung-Hoon; Noh, Jin-Yong; Gomis, Susantha; Song, Chang-Seon

    2015-08-01

    Ducks are a natural reservoir for H5N1 highly pathogenic avian influenza (HPAI) viruses, which produces a range of clinical outcomes from asymptomatic infections to severe disease with mortality. Vaccination against HPAI is one of the few methods available for controlling avian influenza virus (AIV) infection in domestic ducks; therefore, it is necessary to improve vaccine efficacy against HPAI in domestic ducks. However, few studies have focused on enhancing the immune response by testing alternative administration routes and adjuvants. While attempting to maximize the efficacy of a vaccine, it is important to select an appropriate vaccine delivery route and adjuvant to elicit an enhanced immune response. Although several studies have indicated that the vaccination of ducks against HPAI viruses has offered protection against lethal virus challenge, the immunogenicity of the vaccine still requires improvement. In this study, we characterized the immune response following a novel vaccination strategy against H5N1 HPAI virus in domestic ducks. Our novel intradermal delivery system and the application of the cytosine-phosphodiester-guanine (CpG) oligodeoxynucleotide (ODN) adjuvant allowed us to obtain information regarding the sustained vaccine immunity. Compared with the intramuscular route of vaccination, the intradermal route resulted in higher antibody titer as well as lower antibody deviation following secondary vaccination. In addition, the use of a CpG-ODN adjuvant had a dose-sparing effect on antibody titer. Furthermore, when a high dose of antigen was used, the CpG-ODN-adjuvanted vaccine maintained a high mean antibody titer. This data demonstrates that intradermal immunization combined with administration of CpG-ODN as an adjuvant may be a promising strategy for improving vaccine efficacy in domestic ducks. PMID:26069254

  1. Identification of Disubstituted Sulfonamide Compounds as Specific Inhibitors of Hepatitis B Virus Covalently Closed Circular DNA Formation

    PubMed Central

    Cai, Dawei; Mills, Courtney; Yu, Wenquan; Yan, Ran; Aldrich, Carol E.; Saputelli, Jeffry R.; Mason, William S.; Xu, Xiaodong; Guo, Ju-Tao; Block, Timothy M.

    2012-01-01

    Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) plays a central role in viral infection and persistence and is the basis for viral rebound after the cessation of therapy, as well as the elusiveness of a cure even after extended treatment. Therefore, there is an urgent need for the development of novel therapeutic agents that directly target cccDNA formation and maintenance. By employing an innovative cell-based cccDNA assay in which secreted HBV e antigen is a cccDNA-dependent surrogate, we screened an in-house small-molecule library consisting of 85,000 drug-like compounds. Two structurally related disubstituted sulfonamides (DSS), termed CCC-0975 and CCC-0346, emerged and were confirmed as inhibitors of cccDNA production, with low micromolar 50% effective concentrations (EC50s) in cell culture. Further mechanistic studies demonstrated that DSS compound treatment neither directly inhibited HBV DNA replication in cell culture nor reduced viral polymerase activity in the in vitro endogenous polymerase assay but synchronously reduced the levels of HBV cccDNA and its putative precursor, deproteinized relaxed circular DNA (DP-rcDNA). However, DSS compounds did not promote the intracellular decay of HBV DP-rcDNA and cccDNA, suggesting that the compounds interfere primarily with rcDNA conversion into cccDNA. In addition, we demonstrated that CCC-0975 was able to reduce cccDNA biosynthesis in duck HBV-infected primary duck hepatocytes. This is the first attempt, to our knowledge, to identify small molecules that target cccDNA formation, and DSS compounds thus potentially serve as proof-of-concept drug candidates for development into therapeutics to eliminate cccDNA from chronic HBV infection. PMID:22644022

  2. Isothiafludine, a novel non-nucleoside compound, inhibits hepatitis B virus replication through blocking pregenomic RNA encapsidation

    PubMed Central

    Yang, Li; Shi, Li-ping; Chen, Hai-jun; Tong, Xian-Kun; Wang, Gui-feng; Zhang, Yang-ming; Wang, Wen-long; Feng, Chun-lan; He, Pei-lan; Zhu, Feng-hua; Hao, You-hua; Wang, Bao-ju; Yang, Dong-liang; Tang, Wei; Nan, Fa-jun; Zuo, Jian-ping

    2014-01-01

    Aim: To investigate the action of isothiafludine (NZ-4), a derivative of bis-heterocycle tandem pairs from the natural product leucamide A, on the replication cycle of hepatitis B virus (HBV) in vitro and in vivo. Methods: HBV replication cycle was monitored in HepG2.2.15 cells using qPCR, qRT-PCR, and Southern and Northern blotting. HBV protein expression and capsid assembly were detected using Western blotting and native agarose gel electrophoresis analysis. The interaction of pregenomic RNA (pgRNA) and the core protein was investigated by RNA immunoprecipitation. To evaluate the anti-HBV effect of NZ-4 in vivo, DHBV-infected ducks were orally administered NZ-4 (25, 50 or 100 mg·kg−1·d−1) for 15 d. Results: NZ-4 suppressed intracellular HBV replication in HepG2.2.15 cells with an IC50 value of 1.33 μmol/L, whereas the compound inhibited the cell viability with an IC50 value of 50.4 μmol/L. Furthermore, NZ-4 was active against the replication of various drug-resistant HBV mutants, including 3TC/ETV-dual-resistant and ADV-resistant HBV mutants. NZ-4 (5, 10, 20 μmol/L) concentration-dependently reduced the encapsidated HBV pgRNA, resulting in the assembly of replication-deficient capsids in HepG2.2.15 cells. Oral administration of NZ-4 dose-dependently inhibited DHBV DNA replication in the DHBV-infected ducks. Conclusion: NZ-4 inhibits HBV replication by interfering with the interaction between pgRNA and HBcAg in the capsid assembly process, thus increasing the replication-deficient HBV capsids. Such mechanism of action might provide a new therapeutic strategy to combat HBV infection. PMID:24487969

  3. Hepatitis C virus-host interactions: Etiopathogenesis and therapeutic strategies

    PubMed Central

    Hassan, Mohamed; Selimovic, Denis; El-Khattouti, Abdelouahid; Ghozlan, Hanan; Haikel, Youssef; Abdelkader, Ola

    2012-01-01

    Hepatitis C virus (HCV) is a significant health problem facing the world. This virus infects more than 170 million people worldwide and is considered the major cause of both acute and chronic hepatitis. Persons become infected mainly through parenteral exposure to infected material by blood transfusions or injections with nonsterile needles. Although the sexual behavior is considered as a high risk factor for HCV infection, the transmission of HCV infection through sexual means, is less frequently. Currently, the available treatment for patients with chronic HCV infection is interferon based therapies alone or in combination with ribavirin and protease inhibitors. Although a sustained virological response of patients to the applied therapy, a great portion of patients did not show any response. HCV infection is mostly associated with progressive liver diseases including fibrosis, cirrhosis and hepatocellular carcinoma. Although the focus of many patients and clinicians is sometimes limited to that problem, the natural history of HCV infection (HCV) is also associated with the development of several extrahepatic manifestations including dermatologic, rheumatologic, neurologic, and nephrologic complications, diabetes, arterial hypertension, autoantibodies and cryglobulins. Despite the notion that HCV-mediated extrahepatic manifestations are credible, the mechanism of their modulation is not fully described in detail. Therefore, the understanding of the molecular mechanisms of HCV-induced alteration of intracellular signal transduction pathways, during the course of HCV infection, may offer novel therapeutic targets for HCV-associated both hepatic and extrahepatic manifestations. This review will elaborate the etiopathogenesis of HCV-host interactions and summarize the current knowledge of HCV-associated diseases and their possible therapeutic strategies. PMID:24520529

  4. Asymptomatic Hepadnaviral Persistence and Its Consequences in the Woodchuck Model of Occult Hepatitis B Virus Infection

    PubMed Central

    Mulrooney-Cousins, Patricia M.; Michalak, Tomasz I.

    2015-01-01

    Woodchuck hepatitis virus (WHV) is molecularly and pathogenically closely related to hepatitis B virus (HBV). Both viruses display tropism towards hepatocytes and cells of the immune system and cause similar liver pathology, where acute hepatitis can progress to chronic hepatitis and to hepatocellular carcinoma (HCC). Two forms of occult hepadnaviral persistence were identified in the woodchuck-WHV model: secondary occult infection (SOI) and primary occult infection (POI). SOI occurs after resolution of a serologically apparent infection with hepatitis or after subclinical serologically evident virus exposure. POI is caused by small amounts of virus and progresses without serological infection markers, but the virus genome and its replication are detectable in the immune system and with time in the liver. SOI can be accompanied by minimal hepatitis, while the hallmark of POI is normal liver morphology. Nonetheless, HCC develops in about 20% of animals with SOI or POI within 3 to 5 years. The virus persists throughout the lifespan in both SOI and POI at serum levels rarely greater than 100 copies/mL, causes hepatitis and HCC when concentrated and administered to virus-naïve woodchucks. SOI is accompanied by virus-specific T and B cell immune responses, while only virus-specific T cells are detected in POI. SOI coincides with protection against reinfection, while POI does not and hepatitis develops after challenge with liver pathogenic doses >1000 virions. Both SOI and POI are associated with virus DNA integration into the liver and the immune system genomes. Overall, SOI and POI are two distinct forms of silent hepadnaviral persistence that share common characteristics. Here, we review findings from the woodchuck model and discuss the relevant observations made in human occult HBV infection (OBI). PMID:26623268

  5. Coinfection of hepatic cell lines with human immunodeficiency virus and hepatitis B virus leads to an increase in intracellular hepatitis B surface antigen.

    PubMed

    Iser, David M; Warner, Nadia; Revill, Peter A; Solomon, Ajantha; Wightman, Fiona; Saleh, Suha; Crane, Megan; Cameron, Paul U; Bowden, Scott; Nguyen, Tin; Pereira, Cândida F; Desmond, Paul V; Locarnini, Stephen A; Lewin, Sharon R

    2010-06-01

    Liver-related mortality is increased in the setting of HIV-hepatitis B virus (HBV) coinfection. However, interactions between HIV and HBV to explain this observation have not been described. We hypothesized that HIV infection of hepatocytes directly affects the life cycle of HBV. We infected human hepatic cell lines expressing HBV (Hep3B and AD38 cells) or not expressing HBV (Huh7, HepG2, and AD43 cells) with laboratory strains of HIV (NL4-3 and AD8), as well as a vesicular stomatitis virus (VSV)-pseudotyped HIV expressing enhanced green fluorescent protein (EGFP). Following HIV infection with NL4-3 or AD8 in hepatic cell lines, we observed a significant increase in HIV reverse transcriptase activity which was infectious. Despite no detection of surface CD4, CCR5, and CXCR4 by flow cytometry, AD8 infection of AD38 cells was inhibited by maraviroc and NL4-3 was inhibited by AMD3100, demonstrating that HIV enters AD38 hepatic cell lines via CCR5 or CXCR4. High-level infection of AD38 cells (50%) was achieved using VSV-pseudotyped HIV. Coinfection of the AD38 cell line with HIV did not alter the HBV DNA amount or species as determined by Southern blotting or nucleic acid signal amplification. However, coinfection with HIV was associated with a significant increase in intracellular HBsAg when measured by Western blotting, quantitative HBsAg, and fluorescence microscopy. We conclude that HIV infection of HBV-infected hepatic cell lines significantly increased intracellular HBsAg but not HBV DNA synthesis and that increased intrahepatic HBsAg secondary to direct infection by HIV may contribute to accelerated liver disease in HIV-HBV-coinfected individuals. PMID:20357083

  6. Virus-Like Vesicle-Based Therapeutic Vaccine Vectors for Chronic Hepatitis B Virus Infection

    PubMed Central

    Reynolds, Tracy D.; Buonocore, Linda; Rose, Nina F.; Rose, John K.

    2015-01-01

    ABSTRACT More than 500,000 people die each year from the liver diseases that result from chronic hepatitis B virus (HBV) infection. Therapeutic vaccines, which aim to elicit an immune response capable of controlling the virus, offer a potential new treatment strategy for chronic hepatitis B. Recently, an evolved, high-titer vaccine platform consisting of Semliki Forest virus RNA replicons that express the vesicular stomatitis virus glycoprotein (VSV G) has been described. This platform generates virus-like vesicles (VLVs) that contain VSV G but no other viral structural proteins. We report here that the evolved VLV vector engineered to additionally express the HBV middle surface envelope glycoprotein (MHBs) induces functional CD8 T cell responses in mice. These responses were greater in magnitude and broader in specificity than those obtained with other immunization strategies, including recombinant protein and DNA. Additionally, a single immunization with VLV-MHBs protected mice from HBV hydrodynamic challenge, and this protection correlated with the elicitation of a CD8 T cell recall response. In contrast to MHBs, a VLV expressing HBV core protein (HBcAg) neither induced a CD8 T cell response in mice nor protected against challenge. Finally, combining DNA and VLV-MHBs immunization led to induction of HBV-specific CD8 T cell responses in a transgenic mouse model of chronic HBV infection. The ability of VLV-MHBs to induce a multispecific T cell response capable of controlling HBV replication, and to generate immune responses in a tolerogenic model of chronic infection, indicates that VLV vaccine platforms may offer a unique strategy for HBV therapeutic vaccination. IMPORTANCE HBV infection is associated with significant morbidity and mortality. Furthermore, treatments for chronic infection are suboptimal and rarely result in complete elimination of the virus. Therapeutic vaccines represent a unique approach to HBV treatment and have the potential to induce long

  7. Avian Influenza Ecology in North Atlantic Sea Ducks: Not All Ducks Are Created Equal

    PubMed Central

    Hall, Jeffrey S.; Russell, Robin E.; Franson, J. Christian; Soos, Catherine; Dusek, Robert J.; Allen, R. Bradford; Nashold, Sean W.; TeSlaa, Joshua L.; Jónsson, Jón Eínar; Ballard, Jennifer R.; Harms, Naomi Jane; Brown, Justin D.

    2015-01-01

    Wild waterfowl are primary reservoirs of avian influenza viruses (AIV). However the role of sea ducks in the ecology of avian influenza, and how that role differs from freshwater ducks, has not been examined. We obtained and analyzed sera from North Atlantic sea ducks and determined the seroprevalence in those populations. We also tested swab samples from North Atlantic sea ducks for the presence of AIV. We found relatively high serological prevalence (61%) in these sea duck populations but low virus prevalence (0.3%). Using these data we estimated that an antibody half-life of 141 weeks (3.2 years) would be required to attain these prevalences. These findings are much different than what is known in freshwater waterfowl and have implications for surveillance efforts, AIV in marine environments, and the roles of sea ducks and other long-lived waterfowl in avian influenza ecology. PMID:26677841

  8. Avian influenza ecology in North Atlantic sea ducks: Not all ducks are created equal

    USGS Publications Warehouse

    Hall, Jeffrey S.; Russell, Robin E.; Franson, J. Christian; Soos, Catherine; Dusek, Robert J.; Allen, R. Bradford; Nashold, Sean W.; Teslaa, Joshua L.; Jónsson, Jón Einar; Ballard, Jennifer R.; Harms, Naomi Jnae; Brown, Justin D.

    2015-01-01

    Wild waterfowl are primary reservoirs of avian influenza viruses (AIV). However the role of sea ducks in the ecology of avian influenza, and how that role differs from freshwater ducks, has not been examined. We obtained and analyzed sera from North Atlantic sea ducks and determined the seroprevalence in those populations. We also tested swab samples from North Atlantic sea ducks for the presence of AIV. We found relatively high serological prevalence (61%) in these sea duck populations but low virus prevalence (0.3%). Using these data we estimated that an antibody half-life of 141 weeks (3.2 years) would be required to attain these prevalences. These findings are much different than what is known in freshwater waterfowl and have implications for surveillance efforts, AIV in marine environments, and the roles of sea ducks and other long-lived waterfowl in avian influenza ecology.

  9. Comparative analysis of transcriptional profiles of retinoic-acid-induced gene I-like receptors and interferons in seven tissues from ducks infected with avian Tembusu virus.

    PubMed

    Fu, Guanghua; Chen, Cuiteng; Huang, Yu; Cheng, Longfei; Fu, Qiuling; Wan, Chunhe; Shi, Shaohua; Chen, Hongmei; Liu, Wei

    2016-01-01

    Avian Tembusu virus (ATV), an emerging virus that mainly infects laying and breeding ducks in China, has caused severe economic loss in duck industry. However, there have been no reports about host innate immune responses during ATV infection and its correlation with clinical signs or pathology. To identify the roles of these immune factors in the innate host response to ATV infection, quantitative real-time PCR (qPCR) was used to analyze the transcriptional profiles on the genes encoding two retinoic-acid-induced gene I (RIG-I)-like receptors (RLRs) and two interferons (INF-α and INF-γ) in seven tissues of an ATV-infected shelduck. After infection with ATV, both RLR genes were significantly upregulated (P < 0.05) in all seven tissues. The peak expression levels of the two RLR genes were observed at 24 hours postinfection (hpi) and were higher in non-lymphoid tissues (liver, lung, kidney, and ovary) than in lymphoid tissues (thymus, spleen and bursa). Although the transcription levels of both IFN genes were also upregulated, they showed different time-dependent expression patterns compared with those of the RLR genes. In addition, the highest mRNA expression of the two IFN genes was observed in the ovary at 6 hpi. This observation suggests that the ovary is the primary target tissue in ATV infection and explains the clinical characteristics of the primary pathological changes in the ovaries of ATV-infected ducks. Our results, for the first time, elucidate the differential and coordinated expression profiles of two RLRs and two IFNs in an ATV-infected shelduck. PMID:26427380

  10. Hepatitis C virus markers in infection by hepatitis C virus: In the era of directly acting antivirals

    PubMed Central

    Coppola, Nicola; Pisaturo, Mariantonietta; Zampino, Rosa; Macera, Margherita; Sagnelli, Caterina; Sagnelli, Evangelista

    2015-01-01

    About 130-170 million people are infected with the hepatitis C virus (HCV) worldwide and more than 350000 people die each year of HCV-related liver diseases. The combination of pegylated interferon (Peg-IFN) and ribavirin (RBV) was recommended as the treatment of choice for chronic hepatitis C for nearly a decade. In 2011 the directly acting antivirals (DAA) HCV NS3/4A protease inhibitors, telaprevir and boceprevir, were approved to treat HCV-genotype-1 infection, each in triple combination with Peg-IFN and RBV. These treatments allowed higher rates of SVR than the double Peg-IFN + RBV, but the low tolerability and high pill burden of these triple regimes were responsible for reduced adherence and early treatment discontinuation. The second and third wave DAAs introduced in 2013-2014 enhanced the efficacy and tolerability of anti-HCV treatment. Consequently, the traditional indicators for disease management and predictors of treatment response should be revised in light of these new therapeutic options. This review article will focus on the use of the markers of HCV infection and replication, of laboratory and instrumental data to define the stage of the disease and of predictors, if any, of response to therapy in the DAA era. The article is addressed particularly to physicians who have patients with hepatitis C in care in their everyday clinical practice. PMID:26478667

  11. Virus-specific mRNA capping enzyme encoded by hepatitis E virus.

    PubMed

    Magden, J; Takeda, N; Li, T; Auvinen, P; Ahola, T; Miyamura, T; Merits, A; Kääriäinen, L

    2001-07-01

    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. PMID:11413290

  12. Individual donor-nucleic acid testing for human immunodeficiency virus-1, hepatitis C virus and hepatitis B virus and its role in blood safety

    PubMed Central

    Kumar, Rajesh; Gupta, Sonia; Kaur, Amarjit; Gupta, Manvi

    2015-01-01

    Background: Transfusion-transmitted infections (TTIs) are one of the biggest threats to blood transfusion safety. Nucleic acid testing (NAT) in blood donor screening has been implemented in many countries to reduce the risk of TTIs. NAT shortens this window period, thereby offering blood centers a much higher sensitivity for detecting viral infections. Aims: The objective was to assess the role of individual donor-NAT (ID-NAT) for human immunodeficiency virus-1 (HIV-1), hepatitis C virus (HCV) and hepatitis B virus (HBV) and its role in blood safety. Materials and Methods: A total of 32978 donations were tested for all three viruses using enzyme-linked immuno-sorbent assay (Vironostika® HIV Ag-Ab, Hepanostika® HCV ultra and hepatitis B surface antigen ultra by Biomerieux) and ID-NAT using Procleix Ultrio plus® Assay (Novartis Diagnostic, USA). All initial NAT reactive samples and serology nonreactive were retested in triplicate and NAT discriminatory assay for HIV-1, HCV and HBV were performed. Results: Of the 32978 samples, 43 (0.13%) were found to be ID-NAT reactive but seronegative. Out of 43, one for HIV-1, 13 for HCV and 27 for HBV were reactive by discriminatory assays. There were two samples that were reactive for both HCV-HBV and counted as HCV-HBV co-infection NAT yield. The prevalence of these viruses in our sample, tested by ID-NAT is 0.06%, 0.71%, and 0.63% for HIV-1, HCV and HBV respectively. The combined NAT yield among blood donors was 1 in 753. Conclusion: ID-NAT testing for HIV-1, HCV and HBV can tremendously improve the efficacy of screening for protecting blood recipient from TTIs. It enables detection of these viruses that were undetected by serological test and thus helped in providing safe blood to the patients. PMID:26420945

  13. Evolutionary origins of hepatitis A virus in small mammals.

    PubMed

    Drexler, Jan Felix; Corman, Victor M; Lukashev, Alexander N; van den Brand, Judith M A; Gmyl, Anatoly P; Brünink, Sebastian; Rasche, Andrea; Seggewiβ, Nicole; Feng, Hui; Leijten, Lonneke M; Vallo, Peter; Kuiken, Thijs; Dotzauer, Andreas; Ulrich, Rainer G; Lemon, Stanley M; Drosten, Christian

    2015-12-01

    Hepatitis A virus (HAV) is an ancient and ubiquitous human pathogen recovered previously only from primates. The sole species of the genus Hepatovirus, existing in both enveloped and nonenveloped forms, and with a capsid structure intermediate between that of insect viruses and mammalian picornaviruses, HAV is enigmatic in its origins. We conducted a targeted search for hepatoviruses in 15,987 specimens collected from 209 small mammal species globally and discovered highly diversified viruses in bats, rodents, hedgehogs, and shrews, which by pairwise sequence distance comprise 13 novel Hepatovirus species. Near-complete genomes from nine of these species show conservation of unique hepatovirus features, including predicted internal ribosome entry site structure, a truncated VP4 capsid protein lacking N-terminal myristoylation, a carboxyl-terminal pX extension of VP1, VP2 late domains involved in membrane envelopment, and a cis-acting replication element within the 3D(pol) sequence. Antibodies in some bat sera immunoprecipitated and neutralized human HAV, suggesting conservation of critical antigenic determinants. Limited phylogenetic cosegregation among hepatoviruses and their hosts and recombination patterns are indicative of major hepatovirus host shifts in the past. Ancestral state reconstructions suggest a Hepatovirus origin in small insectivorous mammals and a rodent origin of human HAV. Patterns of infection in small mammals mimicked those of human HAV in hepatotropism, fecal shedding, acute nature, and extinction of the virus in a closed host population. The evolutionary conservation of hepatovirus structure and pathogenesis provide novel insight into the origins of HAV and highlight the utility of analyzing animal reservoirs for risk assessment of emerging viruses. PMID:26575627

  14. Involvement of ESCRT-II in Hepatitis B Virus Morphogenesis

    PubMed Central

    Stieler, Jens T.; Prange, Reinhild

    2014-01-01

    The hepatitis B virus (HBV) is an enveloped DNA virus that replicates via reverse transcription of its pregenomic RNA (pgRNA). Budding of HBV is supposed to occur at intracellular membranes and requires scission functions of the endosomal sorting complex required for transport (ESCRT) provided by ESCRT-III and VPS4. Here, we have investigated the impact of the upstream-acting ESCRT-I and ESCRT-II complexes in HBV morphogenesis. RNA interference knockdown of the ESCRT-I subunits TSG101 and VPS28 did not block, but rather stimulate virus release. In contrast, RNAi-mediated depletion of the ESCRT-II components EAP20, EAP30 and EAP45 greatly reduced virus egress. By analyzing different steps of the HBV maturation pathway, we find that the knockdown of ESCRT-II not only inhibited the production and/or release of enveloped virions, but also impaired intracellular nucleocapsid formation. Transcription/translation studies revealed that the depletion of ESCRT-II neither affected the synthesis and nuclear export of HBV-specific RNAs nor the expression of the viral core and envelope proteins. Moreover, the absence of ESCRT-II had no effects on the assembly capability and integrity of HBV core/capsids. However, the level of encapsidated pgRNA was significantly reduced in ESCRT-II-depleted cells, implicating that ESCRT-II directs steps accompanying the formation of replication-competent nucleocapsids, like e.g. assisting in RNA trafficking and encapsidation. In support of this, the capsid protein was found to interact and colocalize with ESCRT-II subunits in virus-producing cells. Together, these results indicate an essential role for ESCRT-II in the HBV life cycle and suggest that ESCRT-II functions prior to the final HBV budding reaction. PMID:24614091

  15. Evolutionary origins of hepatitis A virus in small mammals

    PubMed Central

    Drexler, Jan Felix; Corman, Victor M.; Lukashev, Alexander N.; van den Brand, Judith M. A.; Gmyl, Anatoly P.; Brünink, Sebastian; Rasche, Andrea; Seggewiβ, Nicole; Feng, Hui; Leijten, Lonneke M.; Vallo, Peter; Kuiken, Thijs; Dotzauer, Andreas; Ulrich, Rainer G.; Lemon, Stanley M.; Drosten, Christian

    2015-01-01

    Hepatitis A virus (HAV) is an ancient and ubiquitous human pathogen recovered previously only from primates. The sole species of the genus Hepatovirus, existing in both enveloped and nonenveloped forms, and with a capsid structure intermediate between that of insect viruses and mammalian picornaviruses, HAV is enigmatic in its origins. We conducted a targeted search for hepatoviruses in 15,987 specimens collected from 209 small mammal species globally and discovered highly diversified viruses in bats, rodents, hedgehogs, and shrews, which by pairwise sequence distance comprise 13 novel Hepatovirus species. Near-complete genomes from nine of these species show conservation of unique hepatovirus features, including predicted internal ribosome entry site structure, a truncated VP4 capsid protein lacking N-terminal myristoylation, a carboxyl-terminal pX extension of VP1, VP2 late domains involved in membrane envelopment, and a cis-acting replication element within the 3Dpol sequence. Antibodies in some bat sera immunoprecipitated and neutralized human HAV, suggesting conservation of critical antigenic determinants. Limited phylogenetic cosegregation among hepatoviruses and their hosts and recombination patterns are indicative of major hepatovirus host shifts in the past. Ancestral state reconstructions suggest a Hepatovirus origin in small insectivorous mammals and a rodent origin of human HAV. Patterns of infection in small mammals mimicked those of human HAV in hepatotropism, fecal shedding, acute nature, and extinction of the virus in a closed host population. The evolutionary conservation of hepatovirus structure and pathogenesis provide novel insight into the origins of HAV and highlight the utility of analyzing animal reservoirs for risk assessment of emerging viruses. PMID:26575627

  16. Identification of a spliced gene from duck enteritis virus encoding a protein homologous to UL15 of herpes simplex virus 1

    PubMed Central

    2011-01-01

    Background In herpesviruses, UL15 homologue is a subunit of terminase complex responsible for cleavage and packaging of the viral genome into pre-assembled capsids. However, for duck enteritis virus (DEV), the causative agent of duck viral enteritis (DVE), the genomic sequence was not completely determined until most recently. There is limited information of this putative spliced gene and its encoding protein. Results DEV UL15 consists of two exons with a 3.5 kilobases (kb) inron and transcribes into two transcripts: the full-length UL15 and an N-terminally truncated UL15.5. The 2.9 kb UL15 transcript encodes a protein of 739 amino acids with an approximate molecular mass of 82 kiloDaltons (kDa), whereas the UL15.5 transcript is 1.3 kb in length, containing a putative 888 base pairs (bp) ORF that encodes a 32 kDa product. We also demonstrated that UL15 gene belonged to the late kinetic class as its expression was sensitive to cycloheximide and phosphonoacetic acid. UL15 is highly conserved within the Herpesviridae, and contains Walker A and B motifs homologous to the catalytic subunit of the bacteriophage terminase as revealed by sequence analysis. Phylogenetic tree constructed with the amino acid sequences of 23 herpesvirus UL15 homologues suggests a close relationship of DEV to the Mardivirus genus within the Alphaherpesvirinae. Further, the UL15 and UL15.5 proteins can be detected in the infected cell lysate but not in the sucrose density gradient-purified virion when reacting with the antiserum against UL15. Within the CEF cells, the UL15 and/or UL15.5 localize(s) in the cytoplasm at 6 h post infection (h p. i.) and mainly in the nucleus at 12 h p. i. and at 24 h p. i., while accumulate(s) in the cytoplasm in the absence of any other viral protein. Conclusions DEV UL15 is a spliced gene that encodes two products encoded by 2.9 and 1.3 kb transcripts respectively. The UL15 is expressed late during infection. The coding sequences of DEV UL15 are very similar to

  17. High prevalence of occult hepatitis B virus genotype H infection among children with clinical hepatitis in west Mexico

    PubMed Central

    Escobedo-Melendez, Griselda; Panduro, Arturo; Fierro, Nora A; Roman, Sonia

    2014-01-01

    Studies on the prevalence of infection with hepatitis B virus (HBV) among children are scarce in Latin American countries, especially in Mexico. This study was aimed to investigate the prevalence of HBV infection, occult hepatitis B infection (OBI) and HBV genotypes among children with clinical hepatitis. In total, 215 children with clinical hepatitis were evaluated for HBV infection. HBV serological markers and HBV DNA were analysed. OBI diagnosis and HBV genotyping was performed. HBV infection was found in 11.2% of children with clinical hepatitis. Among these HBV DNA positive-infected children, OBI was identified in 87.5% (n = 21/24) of the cases and 12.5% (n = 3/24) were positive for both HBV DNA and hepatitis B surface antigen. OBI was more frequent among children who had not been vaccinated against hepatitis B (p < 0.05) than in those who had been vaccinated. HBV genotype H was prevalent in 71% of the children followed by genotype G (8%) and genotype A (4%). In conclusion, OBI is common among Mexican children with clinical hepatitis and is associated with HBV genotype H. The results show the importance of the molecular diagnosis of HBV infection in Mexican paediatric patients with clinical hepatitis and emphasise the necessity of reinforcing hepatitis B vaccination in children. PMID:25099333

  18. Hepatitis C virus: How genetic variability affects pathobiology of disease.

    PubMed

    Chayama, Kazuaki; Hayes, C Nelson

    2011-01-01

    As an RNA virus, hepatitis C virus (HCV) shows a characteristically high level of nucleotide diversity. Accumulation of nucleotide substitutions in the virus has resulted in diversification into quasispecies, subtypes and distinct genotypes. Pathobiological studies linking nucleotide and amino acid sequences with clinical findings have identified relationships between certain genotypes and characteristic biological properties. Genotype 3 HCV infection was found to be associated with a high level of liver steatosis. Genotypes 1 and 4 were found to be more resistant to interferon (IFN) based therapies than genotypes 2 and 3. Studies of genotype 1 sequences obtained from patients treated with IFN have identified a relationship between favorable response to interferon therapy and amino acid substitutions in the NS5A region (interferon response determining region; ISDR). Further studies have identified a relationship between the effect of IFN therapy and other regions of the NS5A protein. More recently, a relationship has been found between poor response to peg-IFN plus ribavirin combination therapy and substitutions at amino acid 70 and 91 in the core protein. Furthermore, a correlation between human genetic variation in the IL28B (IFN-lamda 3) locus and core amino acid substitutions has been characterized. In this review we briefly summarize the discovery, classification and nomenclature of HCV genotypes and subtypes. We also discuss amino acid substitutions within specific regions that have been reported to be associated with outcome of IFN and peg-IFN plus ribavirin combination therapy. PMID:21199518

  19. Hepatitis C virus RNA functionally sequesters miR-122

    PubMed Central

    Luna, Joseph M.; Scheel, Troels K. H.; Danino, Tal; Shaw, Katharina S.; Mele, Aldo; Fak, John J.; Nishiuchi, Eiko; Takacs, Constantin N.; Catanese, Maria Teresa; de Jong, Ype P.; Jacobson, Ira M.; Rice, Charles M.; Darnell, Robert B.

    2015-01-01

    Summary Hepatitis C virus uniquely requires the liver specific microRNA-122 for replication, yet global effects on endogenous miRNA targets during infection are unexplored. Here, high-throughput sequencing and crosslinking immunoprecipitation (HITS-CLIP) experiments of human Argonaute (Ago) during HCV infection showed robust Ago binding on the HCV 5′UTR, at known and predicted miR-122 sites. On the human transcriptome, we observed reduced Ago binding and functional mRNA de-repression of miR-122 targets during virus infection. This miR-122 “sponge” effect was relieved and redirected to miR-15 targets by swapping the miRNA tropism of the virus. Single-cell expression data from reporters containing miR-122 sites showed significant de-repression during HCV infection depending on expression level and site number. We describe a quantitative mathematical model of HCV induced miR-122 sequestration and propose that such miR-122 inhibition by HCV RNA may result in global de-repression of host miR-122 targets, providing an environment fertile for the long-term oncogenic potential of HCV. PMID:25768906

  20. Depuration kinetics of hepatitis A virus in clams.

    PubMed

    Polo, David; Ávarez, Cristina; Vilariño, M Luz; Longa, Ángeles; Romalde, Jesús L

    2014-05-01

    The efficacy and dynamic of depuration for the removal of hepatitis A virus (HAV) contamination were evaluated under experimental conditions using Manila clams previously subjected to bioaccumulation with this virus. Five independent trials were assayed in a closed experimental system with a total volume of approximately 1750 l, using clam batches of 60 Kg. The reverse transcriptase-real time PCR (RT-qPCR) technique was utilized for viral quantification. Infectivity assays were conducted at the end of depuration. Although the final viral loads in shellfish after 7 days remained relatively high and still infectious, an average reduction in HAV levels of 1.44 log units (approx. 93.1%) was observed. This reduction showed a two-phase removal kinetic, with an initial rapid reduction of viruses during the first 72 h of depuration, with a 0.6 log units (69%) of average decrease in HAV RNA copies/g digestive tissue, and a subsequent stabilization with a slower depuration rate in the remaining days. PMID:24387859