91 research outputs found

    Hepatitis C virus nonstructural protein 5B is involved in virus morphogenesis

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    The p7 protein of hepatitis C virus (HCV) is a viroporin that is dispensable for viral genome replication but plays a critical role in virus morphogenesis. In this study, we generated a JFH1-based intergenotypic chimeric genome that encoded a heterologous genotype 1b (GT1b) p7. The parental intergenotypic chimeric genome was nonviable in human hepatoma cells, and infectious chimeric virions were produced only when cells transfected with the chimeric genomes were passaged several times. Sequence analysis of the entire polyprotein-coding region of the recovered chimeric virus revealed one predominant amino acid substitution in nonstructural protein 2 (NS2), T23N, and one in NS5B, K151R. Forward genetic analysis demonstrated that each of these mutations per se restored the infectivity of the parental chimeric genome, suggesting that interactions between p7, NS2, and NS5B were required for virion assembly/maturation. p7 and NS5B colocalized in cellular compartments, and the NS5B mutation did not affect the colocalization pattern. The NS5B K151R mutation neither increased viral RNA replication in human hepatoma cells nor altered the polymerase activity of NS5B in an in vitro assay. In conclusion, this study suggests that HCV NS5B is involved in virus morphogenesis.Hamed Gouklani, Rowena A. Bull, Claudia Beyer, Fasséli Coulibaly, Eric J. Gowans, Heidi E. Drummer, Hans J. Netter, Peter A. White and Gholamreza Haqshena

    Hepatitis Delta Virus

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    Temperature dependence of the Ebar-]2abar far-infrared absorption line of excited chromium ions in ruby

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    By using far-infrared laser spectroscopy we have studied the temperature dependence of the absorption that is due to transitions between the E¯(2E) and 2A¯(2E) levels of excited Cr3+ ions in ruby. From the temperature dependence of the linewidth we determined the inhomogeneous and the homogeneous contributions to line broadening. From the homogeneous width the lifetime of the 2A¯ level was obtained. We found that, for emperatures up to 70 K, the lifetime is due mainly to one-phonon relaxation, whereas at higher temperatures another relaxation process, probably a two-phonon Raman process, becomes strong

    Signalome-wide assessment of host cell response to hepatitis C virus

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    Host cell signalling during infection with intracellular pathogens remains poorly understood. Here we report on the use of antibody microarray technology to detect variations in the expression levels and phosphorylation status of host cell signalling proteins during hepatitis C virus (HCV) replication. Following transfection with HCV RNA, the JNK and NF-kappa B pathways are suppressed, while the JAK/STAT5 pathway is activated; furthermore, components of the apoptosis and cell cycle control machineries are affected in the expression and/or phosphorylation status. RNAi-based hit validation identifies components of the JAK/STAT, NF-kappa B, MAPK and calcium-induced pathways as modulators of HCV replication. Selective chemical inhibition of one of the identified targets, the JNK activator kinase MAP4K2, does impair HCV replication. Thus this study provides a comprehensive picture of host cell pathway mobilization by HCV and uncovers potential therapeutic targets. The strategy of identifying targets for anti-infective intervention within the host cell signalome can be applied to any intracellular pathogen.Australian Cancer Research Foundation (ACRF); Victorian Department of Industry, Innovation and Regional Development (DIIRD); Australian Phenomics Network (APN); Australian Government's Education Investment Fund through the Super Science Initiative; Australasian Genomics Technologies Association (AGTA); Brockhoff Foundation; Peter MacCallum Cancer Centre Foundation; EU (ERC HEPCAR); EU (H2020 HEPCENT); NIH [U19-AI123862]; Australian Centre for HIV and Hepatitis Virology Research (ACH2)SCI(E)ARTICLE

    Penicillamine Revisited: Historic Overview and Review of the Clinical Uses and Cutaneous Adverse Effects

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    Penicillamine is a well-known heavy metal chelator, classically used in the treatment of Wilson disease, rheumatoid arthritis, and cystinuria. From a dermatologic standpoint, penicillamine was found to be useful in the treatment of systemic sclerosis. The successful therapeutic uses of penicillamine have been hindered by its numerous adverse effects, both cutaneous and extra-cutaneous. It is a unique drug since it provokes a diversity of dermatologic manifestations that include (1) acute hypersensitivity reactions, (2) dermopathies characterized by elastic fiber abnormalities including elastosis perforans serpiginosa and pseudo-pseudoxanthoma elasticum, (3) autoimmune disorders such as pemphigus and penicillamine-induced lupus erythematosus-like syndrome, and (4) miscellaneous dermatoses that result from undefined mechanisms. 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    Doença Pulmonar Obstrutiva Crônica e Transtornos de Deglutição: revisão de literatura

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    TCC(graduação) - Universidade Federal de Santa Catarina. Centro de Ciências da Saúde. Fonoaudiologia.Introdução: Pelas projeções dos órgãos de saúde e sociedades científicas da área, nas próximas décadas a DPOC será uma das cinco primeiras causas de morte em todo o mundo sendo que no Brasil já é uma das doenças mais incapacitantes e com elevados índices de mortalidade. A DPOC corresponde a presença de obstrução ou limitação crônica do fluxo aéreo, apresentando progressão lenta e irreversível. A respiração é a parte intrínseca e vital no processo de deglutição, porém, é a função mais afetada na DPOC. Objetivo:Realizar uma revisão de literatura visando encontrar artigos que busquem a relação da Doença Pulmonar Obstrutiva Crônica com transtornos de deglutição.Metodologia:Foi conduzida uma busca em artigos nos idiomas PORTUGUES, INGLES e ESPANHOL sobre a relação da Doença Pulmonar Obstrutiva Crônica com transtornos de deglutição, sem limite de tempo, texto na íntegra, tipo de estudo (sem delimitação), população-alvo (adultos) nas bases de dados MEDLINE-PUBMED, LILACS, SCIELO e SCOPUS. As palavras-chave usadas isoladas e em cruzamentos foram: em português: DPOC; transtornos de deglutição, deglutição, disfagia e disfagia orofaríngea; em inglês: COPD, deglutition disorders, swallowing disorders, dysphagia e em espanhol: EPOC e transtornos de Deglución. Resultados: A pesquisa resultou em 224 artigos, destes apenas 18 preencheram os critérios de inclusão, sendo 12 artigos encontrados na base de dados PUBMED, 3 artigos encontrados na base de dados LILACS e 3 na base SCIELO. Conclusão: Há escassez de trabalhos sobre a correlação entre disfagia no paciente com DPOC, porém, em 15 (quinze) dos 18 (dezoito) artigos estudados, o que corresponde a 79% do total, houve esta relação. Sugerem-se novos estudos, estruturados metodologicamente, abordando este mesmo tema, para a disseminação do conhecimento a cerca dos fatores que podem influenciar a estabilidade do paciente acometido por estas comorbidades.Introduction: According to projections of health agencies and scientific societies of the area in the coming decades COPD is one of the five leading causes of death worldwide and in Brazil is already one of the most disabling diseases and high mortality. COPD accounts for obstruction or chronic airflow limitation, with slow progression and irreversible. Breathing is a vital and intrinsic part of the swallowing process, however, is the most affected function in COPD. Objective:To review the literature in order to find articles that seek the relationship of Chronic Obstructive Pulmonary Disease with swallowing disorders. Methods: We conducted a search for articles in languages PORTUGUESE, ENGLISH and SPANISH on the relationship of Chronic Obstructive Pulmonary Disease with swallowing disorders, no time limit, full text, type of study (without boundary), the target population (adults ) in MEDLINE, PUBMED, LILACS, SCIELO and SCOPUS. The keywords used were isolated and crossings: in Portuguese: COPD; swallowing disorders, swallowing, dysphagia and oropharyngeal dysphagia, in English: COPD, deglutition disorders, swallowing disorders, dysphagia and Spanish: EPOC and disorders Deglución. Results:The search resulted in 224 articles, of which only 18 met the inclusion criteria, 12articles found in PUBMED database, 3 articles found in the database LILACS and SCIELO third base. In SCOPUS database items found were discarded due to the exclusion criteria. Conclusion:There are few studies on the correlation between dysphagia in patients with COPD, however, within fifteen (15) of the eighteen (18) items studied, which corresponds to 79% of the total, there was this relationship. Suggest new studies, methodologically structured, addressing the same subject, for the dissemination of knowledge about the factors that may influence the stability of patients affected by these comorbidities

    Immunological response to parenteral vaccination with recombinant hepatitis B virus surface antigen virus-like particles expressing Helicobacter pylori KatA epitopes in a murine H. pylori challenge model

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    Virus-like particles (VLPs) based on the small envelope protein of hepatitis B virus (HBsAg-S) are immunogenic at the B-and T-cell level. In this study, we inserted overlapping sequences encoding the carboxy terminus of the Helicobacter pylori katA gene product into HBsAg-S. The HBsAg-S-KatA fusion proteins were able to assemble into secretion-competent VLPs (VLP-KatA). The VLP-KatA proteins were able to induce KatA-specific antibodies in immunized mice. The mean total IgG antibody titers 41 days post-primary immunization with VLP-KatA (2.3 x 10(3)) were significantly greater (
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