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  1 / 2546 MEDLINE  
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[PMID]:28453178
[Au] Autor:Nasrallah GK; Al Absi ES; Ghandour R; Ali NH; Taleb S; Hedaya L; Ali F; Huwaidy M; Husseini A
[Ad] Endereço:Department of Biomedical Sciences.
[Ti] Título:Seroprevalence of hepatitis E virus among blood donors in Qatar (2013-2016).
[So] Source:Transfusion;57(7):1801-1807, 2017 07.
[Is] ISSN:1537-2995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Hepatitis E virus (HEV) is an RNA virus transmitted mainly through zoonotic transmission or fecal-oral route. More than 80% of Qatar's population are expatriates, including many coming from hyperendemic countries; thus, it is important to estimate the seroprevalence and to compare between different nationalities. The results can be useful in alerting blood banks to the importance of HEV screening. STUDY DESIGN AND METHODS: Samples from 5854 blood donations provided by Hamad Medical Corporation were tested in the period between June 2013 to June 2016. Samples were tested for the presence of anti-HEV immunoglobulin (Ig)G and IgM antibodies and viral RNA using real-time polymerase chain reaction (PCR). Descriptive statistics, bivariate analysis, and multivariate logistic regression were used. RESULTS: Anti-HEV seroprevalence was 20.7%. A total of 1198 and 38 donations tested positive for IgG and IgM antibodies, respectively. Of the IgM-positive donations four tested positive by PCR. A significant association was detected between HEV seroprevalence with age and nationality. CONCLUSION: The seroprevalence of anti-HEV was high in Qatar. Since HEV IgM and RNA were detected, this suggests the possibility of HEV transmission by transfusion. Blood banks in Qatar and the region should consider screening for HEV, especially when transfusion is intended to pregnant women or immunocompromised patients.
[Mh] Termos MeSH primário: Doadores de Sangue
Anticorpos Anti-Hepatite/sangue
Vírus da Hepatite E/isolamento & purificação
[Mh] Termos MeSH secundário: Seres Humanos
Imunoglobulina G/sangue
Imunoglobulina M/sangue
Modelos Logísticos
Estudos Soroepidemiológicos
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Hepatitis Antibodies); 0 (Immunoglobulin G); 0 (Immunoglobulin M)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1111/trf.14116


  2 / 2546 MEDLINE  
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[PMID]:29107193
[Au] Autor:Feurer C; Le Roux A; Rossel R; Barnaud E; Dumarest M; Garry P; Pavio N
[Ad] Endereço:IFIP, French Institute for the Pig and Pork Industry, La Motte au Vicomte, B.P. 35104, 35651 Le Rheu, Cedex, France. Electronic address: carole.feurer@ifip.asso.fr.
[Ti] Título:High load of hepatitis E viral RNA in pork livers but absence in pork muscle at French slaughterhouses.
[So] Source:Int J Food Microbiol;264:25-30, 2018 Jan 02.
[Is] ISSN:1879-3460
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Pork ham muscle can be contaminated with HEV via blood vessels during viremia and represents a possible source of human contamination via the consumption of dried ham. This study evaluated the prevalence of HEV RNA in pork ham muscles and pork livers at slaughterhouses. Serology was determined on the corresponding serum samples. The apparent individual seroprevalence rate in the 49 pig farms studied was 59% [55.5%-61.4%]. None of the 1134 ham muscles tested was positive for the presence of HEV. HEV prevalence in paired liver samples was 2.8% with a level of contamination of up to 1.46 10 copies/g. Sequences of viral strains isolated from positive livers belonged to genotype 3 and subtypes 3c, 3e, 3f and 3j. Our results confirmed that raw pork liver food products are a source of risk for humans but they also showed that there is a limited risk of human infection by HEV through the consumption of ham muscle.
[Mh] Termos MeSH primário: Vírus da Hepatite E/isolamento & purificação
Hepatite E/epidemiologia
Músculos/virologia
Carne Vermelha/virologia
Sus scrofa/virologia
Doenças dos Suínos/epidemiologia
[Mh] Termos MeSH secundário: Matadouros
Adulto
Animais
França/epidemiologia
Genótipo
Vírus da Hepatite E/genética
Seres Humanos
Fígado/virologia
RNA Viral/genética
Estudos Soroepidemiológicos
Suínos
Doenças dos Suínos/virologia
Carga Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Viral)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171107
[St] Status:MEDLINE


  3 / 2546 MEDLINE  
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[PMID]:28449278
[Au] Autor:Bansal M; Kaur S; Deka D; Singh R; Gill JPS
[Ad] Endereço:School of Public Health and Zoonoses, GADVASU, Ludhiana, India.
[Ti] Título:Seroepidemiology and molecular characterization of hepatitis E virus infection in swine and occupationally exposed workers in Punjab, India.
[So] Source:Zoonoses Public Health;64(8):662-672, 2017 12.
[Is] ISSN:1863-2378
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Hepatitis E virus (HEV) has two discrete epidemiological patterns: waterborne epidemics in developing countries only, caused by HEV genotype I, and sporadic zoonotic outbreaks in developing and developed countries caused by genotypes III and IV. This study was designed to investigate seroprevalence, molecular detection and the characterization of HEV by nested RT-PCR in swine as well as the occupational risk to exposed human population in Punjab state of north-western India. The occupational risk-exposed group comprised of swine farmers (organized - mixed feed feeders and unorganized - swill feeders), slaughterhouse workers, sewage workers and veterinary internes. During the study period, blood and faecal samples were collected from 320 swine and 360 humans with both high and low occupational exposure risks. The overall seroprevalence of swine HEV was 65.00%, with a significantly higher seropositivity in growing pigs (2-8 months of age). The prevalence of HEV RNA in swine faecal samples by nRT-PCR was 8.75% with a significantly higher detection in swill-fed pigs. With humans in the high occupational exposure risk population, significantly higher anti-HEV IgG seropositivity was observed (60.48%) as compared to control population (10.71%). Strong evidence of association between human anti-HEV IgG seropositivity and certain occupational exposure risk groups was observed (p < 0.05). This indicates that unorganized swine farmers, slaughterhouse workers and sewage workers have higher odds of HEV infection in this study region. Percentage of nucleotide similarity between swine and human HEV isolates was less than that found in countries with zoonotic HEV outbreaks. Molecular characterization revealed the circulation of G IV and G I genotypes among swine and human population in Punjab state, respectively.
[Mh] Termos MeSH primário: Vírus da Hepatite E
Hepatite E/veterinária
Exposição Ocupacional
Doenças dos Suínos/virologia
[Mh] Termos MeSH secundário: Matadouros
Adulto
Animais
Fazendeiros
Fezes/virologia
Hepatite E/epidemiologia
Hepatite E/virologia
Vírus da Hepatite E/genética
Seres Humanos
Índia/epidemiologia
Filogenia
Estudos Soroepidemiológicos
Suínos
Doenças dos Suínos/epidemiologia
Médicos Veterinários
Adulto Jovem
Zoonoses
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180117
[Lr] Data última revisão:
180117
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[St] Status:MEDLINE
[do] DOI:10.1111/zph.12363


  4 / 2546 MEDLINE  
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[PMID]:29176816
[Au] Autor:Spina A; Lenglet A; Beversluis D; de Jong M; Vernier L; Spencer C; Andayi F; Kamau C; Vollmer S; Hogema B; Irwin A; Ngueremi Yary R; Mahamat Ali A; Moussa A; Alfani P; Sang S
[Ad] Endereço:Médecins Sans Frontières, Operational Center Amsterdam (OCA), Ndjamena, Chad.
[Ti] Título:A large outbreak of Hepatitis E virus genotype 1 infection in an urban setting in Chad likely linked to household level transmission factors, 2016-2017.
[So] Source:PLoS One;12(11):e0188240, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: In September 2016, three acutely jaundiced (AJS) pregnant women were admitted to Am Timan Hospital, eastern Chad. We described the outbreak and conducted a case test-negative study to identify risk factors for this genotype of HEV in an acute outbreak setting. METHODS: Active case finding using a community based surveillance network identified suspected AJS cases. Pregnant or visibly ill AJS cases presenting at hospital were tested with Assure® IgM HEV rapid diagnostic tests (RDTs) and some with Polymerase Chain Reaction (PCR) in Amsterdam; confirmed cases were RDT-positive and controls were RDT-negative. All answered questions around: demographics, household makeup, area of residence, handwashing practices, water collection behaviour and clinical presentation. We calculated unadjusted odds ratios (ORs) and 95% confidence intervals (95% CI). RESULTS: Between September and April 2017, 1443 AJS cases (1293 confirmed) were detected in the town(attack rate: 2%; estimated 65,000 population). PCR testing confirmed HEV genotype 1e. HEV RDTs were used for 250 AJS cases; 100 (40%) were confirmed. Risk factors for HEV infection, included: having at least two children under the age of 5 years (OR 2.1, 95%CI 1.1-4.3), having another household member with jaundice (OR 2.4, 95%CI 0.90-6.3) and, with borderline significance, living in the neighbourhoods of Riad (OR 3.8, 95%CI 1.0-1.8) or Ridina (OR 3.3, 95%CI 1.0-12.6). Cases were more likely to present with vomiting (OR 3.2, 9%CI 1.4-7.9) than controls; possibly due to selection bias. Cases were non-significantly less likely to report always washing hands before meals compared with controls (OR 0.33, 95%CI 0.1-1.1). DISCUSSION: Our study suggests household factors and area of residence (possibly linked to access to water and sanitation) play a role in HEV transmission; which could inform future outbreak responses. Ongoing sero-prevalence studies will elucidate more aspects of transmission dynamics of this virus with genotype 1e.
[Mh] Termos MeSH primário: Cidades/estatística & dados numéricos
Surtos de Doenças/estatística & dados numéricos
Características da Família
Vírus da Hepatite E/genética
Hepatite E/epidemiologia
Hepatite E/transmissão
[Mh] Termos MeSH secundário: Adolescente
Adulto
Chade/epidemiologia
Criança
Pré-Escolar
Feminino
Geografia
Seres Humanos
Lactente
Recém-Nascido
Icterícia/epidemiologia
Masculino
Fatores de Risco
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171219
[Lr] Data última revisão:
171219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188240


  5 / 2546 MEDLINE  
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[PMID]:28449246
[Au] Autor:Donnelly MC; Scobie L; Crossan CL; Dalton H; Hayes PC; Simpson KJ
[Ad] Endereço:Department of Hepatology and Scottish Liver Transplant Unit, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh, UK.
[Ti] Título:Review article: hepatitis E-a concise review of virology, epidemiology, clinical presentation and therapy.
[So] Source:Aliment Pharmacol Ther;46(2):126-141, 2017 07.
[Is] ISSN:1365-2036
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Hepatitis E virus (HEV) is a leading cause of acute icteric hepatitis and acute liver failure in the developing world. During the last decade, there has been increasing recognition of autochthonous (locally acquired) HEV infection in developed countries. Chronic HEV infection is now recognised, and in transplant recipients this may lead to cirrhosis and organ failure. AIM: To detail current understanding of the molecular biology of HEV, diagnostic and therapeutic strategies and propose future directions for basic science and clinical research. METHODS: PubMed was searched for English language articles using the key words "hepatitis E", "viral hepatitis", "autochthonous infection", "antiviral therapy", "liver transplantation", "acute", "chronic", "HEV", "genotype", "transmission" "food-borne", "transfusion". Additional relevant publications were identified from article reference lists. RESULTS: There has been increasing recognition of autochthonous HEV infection in Western countries, mainly associated with genotype 3. Chronic HEV infection has been recognised since 2008, and in transplant recipients this may lead to cirrhosis and organ failure. Modes of transmission include food-borne transmission, transfusion of blood products and solid organ transplantation. Ribavirin therapy is used to treat patients with chronic HEV infection, but new therapies are required as there have been reports of treatment failure with ribavirin. CONCLUSIONS: Autochthonous HEV infection is a clinical issue with increasing burden. Future work should focus on increasing awareness of HEV infection in the developed world, emphasising the need for clinicians to have a low threshold for HEV testing, particularly in immunosuppressed patients. Patients at potential risk of chronic HEV infection must also be educated and given advice regarding prevention of infection.
[Mh] Termos MeSH primário: Hepatite E/epidemiologia
Hepatite E/fisiopatologia
[Mh] Termos MeSH secundário: Doença Aguda
Transfusão de Sangue
Doenças Transmitidas por Alimentos/epidemiologia
Doenças Transmitidas por Alimentos/fisiopatologia
Genótipo
Hepatite E/tratamento farmacológico
Hepatite E/virologia
Vírus da Hepatite E/genética
Seres Humanos
Hospedeiro Imunocomprometido
Ribavirina/uso terapêutico
Falha de Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
49717AWG6K (Ribavirin)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171220
[Lr] Data última revisão:
171220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[St] Status:MEDLINE
[do] DOI:10.1111/apt.14109


  6 / 2546 MEDLINE  
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[PMID]:28982029
[Au] Autor:Ahn HS; Han SH; Kim YH; Park BJ; Kim DH; Lee JB; Park SY; Song CS; Lee SW; Choi C; Myoung J; Choi IS
[Ad] Endereço:Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea.
[Ti] Título:Adverse fetal outcomes in pregnant rabbits experimentally infected with rabbit hepatitis E virus.
[So] Source:Virology;512:187-193, 2017 Dec.
[Is] ISSN:1096-0341
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hepatitis E virus (HEV) causes severe hepatitis in pregnant women, with associated poor fetal outcomes. To study HEV viral pathogenesis, pregnant rabbits were infected with low- and high-dose rabbit HEV at 2 weeks gestation. HEV was identified in the serum, feces, and liver tissue of infected rabbits, and dose-dependent fetal mortality rates ranging from 67% to 80% were observed. The aspartate transaminase (AST)/alanine transaminase ratio was significantly higher (P < 0.01) in high-dose infected rabbits than low-dose infected and negative control rabbits 14 days post infection (dpi). Tumor necrosis factor-α (TNF-α) was significantly higher in low-dose (P < 0.01) and high-dose infected rabbits (P < 0.001) than in negative controls 7 dpi. High-dose HEV-infected rabbits produced significantly more interferon-γ (IFN-γ; P < 0.05) than negative control rabbits at 7 and 14 dpi. High levels of AST, TNF-α, and IFN-γ may substantially influence adverse fetal outcomes in pregnant rabbits infected with high-dose HEV.
[Mh] Termos MeSH primário: Vírus da Hepatite E/classificação
Hepatite E/virologia
Hepatite Viral Animal/patologia
Complicações Infecciosas na Gravidez/virologia
Coelhos/anormalidades
[Mh] Termos MeSH secundário: Animais
Anticorpos Antivirais/sangue
Citocinas/genética
Citocinas/metabolismo
Feminino
Regulação da Expressão Gênica/imunologia
Hepatite E/patologia
Vírus da Hepatite E/patogenicidade
Gravidez
Complicações Infecciosas na Gravidez/patologia
Organismos Livres de Patógenos Específicos
Replicação Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Viral); 0 (Cytokines)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171006
[St] Status:MEDLINE


  7 / 2546 MEDLINE  
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[PMID]:28957334
[Au] Autor:Wang H; Zhang W; Gu H; Chen W; Zeng M; Ji C; Song R; Zhang G
[Ad] Endereço:College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province, People's Republic of China.
[Ti] Título:Identification and characterization of two linear epitope motifs in hepatitis E virus ORF2 protein.
[So] Source:PLoS One;12(9):e0184947, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hepatitis E virus (HEV) is responsible for hepatitis E, which represents a global public health problem. HEV genotypes 3 and 4 are reported to be zoonotic, and animals are monitored for HEV infection in the interests of public hygiene and food safety. The development of novel diagnostic methods and vaccines for HEV in humans is thus important topics of research. Opening reading frame (ORF) 2 of HEV includes both linear and conformational epitopes and is regarded as the primary candidate for vaccines and diagnostic tests. We investigated the precise location of the HEV epitopes in the ORF2 protein. We prepared four monoclonal antibodies (mAbs) against genotype 4 ORF2 protein and identified two linear epitopes, G438IVIPHD444 and Y457DNQH461, corresponding to two of these mAbs using phage display biopanning technology. Both these epitopes were speculated to be universal to genotypes 1, 2, 3, 4, and avian HEVs. We also used two 12-mer fragments of ORF2 protein including these two epitopes to develop a peptide-based enzyme-linked immunosorbent assay (ELISA) to detect HEV in serum. This assay demonstrated good specificity but low sensitivity compared with the commercial method, indicating that these two epitopes could serve as potential candidate targets for diagnosis. Overall, these results further our understanding of the epitope distribution of HEV ORF2, and provide important information for the development of peptide-based immunodiagnostic tests to detect HEV in serum.
[Mh] Termos MeSH primário: Epitopos/química
Epitopos/imunologia
Vírus da Hepatite E/imunologia
Proteínas Virais/química
Proteínas Virais/imunologia
[Mh] Termos MeSH secundário: Motivos de Aminoácidos
Sequência de Aminoácidos
Animais
Anticorpos Monoclonais/imunologia
Especificidade de Anticorpos/imunologia
Técnicas de Visualização da Superfície Celular
Células Clonais
Sequência Conservada
Ensaio de Imunoadsorção Enzimática
Genótipo
Vírus da Hepatite E/genética
Camundongos Endogâmicos BALB C
Modelos Moleculares
Peptídeos/química
Alinhamento de Sequência
Suínos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Epitopes); 0 (ORF2 protein, Hepatitis E virus); 0 (Peptides); 0 (Viral Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171018
[Lr] Data última revisão:
171018
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170929
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184947


  8 / 2546 MEDLINE  
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[PMID]:28933680
[Au] Autor:Lassen B; Janson M; Neare K; Tallo T; Reshetnjak I; Kuznetsova T; Viltrop A; Golovljova I; Jokelainen P
[Ad] Endereço:1 Department of Basic Veterinary Sciences and Population Medicine, Institute of Veterinary Medicine and Animal Science, Estonian University of Life Sciences , Tartu, Estonia .
[Ti] Título:Prevalence of Antibodies Against Hepatitis E Virus in Veterinarians in Estonia.
[So] Source:Vector Borne Zoonotic Dis;17(11):773-776, 2017 Nov.
[Is] ISSN:1557-7759
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In this cross-sectional study, we investigated veterinarians in Estonia for evidence of exposure to hepatitis E virus (HEV). In 2012, we collected sera from 158 persons attending a veterinary conference, of whom 156 completed a questionnaire covering their background information. Altogether 115 persons reported they had obtained a veterinary degree and were included in this study. The sera were tested for presence of antibodies against HEV using a commercial enzyme linked immunosorbent assay and a commercial immunoblot assay in series. A sample was considered antibody-positive if it tested positive with both tests. Antibody-positive samples were further examined for the presence of HEV RNA. Three (2.6%) of the 115 veterinarians tested positive for immunoglobulin G antibodies against HEV, whereas no immunoglobulin M antibodies against the virus were detected. The antibody-positive veterinarians were small animal practitioners. Pigs comprised no or small part of their working time or patients. No HEV RNA was detected in the antibody-positive samples. The prevalence of antibodies against HEV in veterinarians in Estonia was lower than what has been observed in veterinarians in other countries.
[Mh] Termos MeSH primário: Anticorpos Antivirais/sangue
Vírus da Hepatite E/imunologia
Hepatite E/imunologia
Exposição Ocupacional
Médicos Veterinários
[Mh] Termos MeSH secundário: Adulto
Animais
Estudos Transversais
Ensaio de Imunoadsorção Enzimática
Estônia/epidemiologia
Feminino
Hepatite E/epidemiologia
Seres Humanos
Immunoblotting
Imunoglobulina G/sangue
Imunoglobulina M/sangue
Masculino
RNA Viral
Estudos Soroepidemiológicos
Zoonoses
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Viral); 0 (Immunoglobulin G); 0 (Immunoglobulin M); 0 (RNA, Viral)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170922
[St] Status:MEDLINE
[do] DOI:10.1089/vbz.2017.2122


  9 / 2546 MEDLINE  
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[PMID]:28878075
[Au] Autor:Nagashima S; Takahashi M; Kobayashi T; Nishizawa T; Nishiyama T; Primadharsini PP; Okamoto H; Tanggis
[Ad] Endereço:Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi, Japan.
[Ti] Título:Characterization of the Quasi-Enveloped Hepatitis E Virus Particles Released by the Cellular Exosomal Pathway.
[So] Source:J Virol;91(22), 2017 Nov 15.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Our previous studies demonstrated that membrane-associated hepatitis E virus (HEV) particles-now considered "quasi-enveloped particles"-are present in the multivesicular body with intraluminal vesicles (exosomes) in infected cells and that the release of HEV virions is related to the exosomal pathway. In this study, we characterized exosomes purified from the culture supernatants of HEV-infected PLC/PRF/5 cells. Purified CD63-, CD9-, or CD81-positive exosomes derived from the culture supernatants of HEV-infected cells that had been cultivated in serum-free medium were found to contain HEV RNA and the viral capsid (ORF2) and ORF3 proteins, as determined by reverse transcription-PCR (RT-PCR) and Western blotting, respectively. Furthermore, immunoelectron microscopy, with or without prior detergent and protease treatment, revealed the presence of virus-like particles in the exosome fraction. These particles were 39.6 ± 1.0 nm in diameter and were covered with a lipid membrane. After treatment with detergent and protease, the diameter of these virus-like particles was 26.9 ± 0.9 nm, and the treated particles became accessible with an anti-HEV ORF2 monoclonal antibody (MAb). The HEV particles in the exosome fraction were capable of infecting naive PLC/PRF/5 cells but were not neutralized by an anti-HEV ORF2 MAb which efficiently neutralizes nonenveloped HEV particles in cell culture. These results indicate that the membrane-wrapped HEV particles released by the exosomal pathway are copurified with the exosomes in the exosome fraction and suggest that the capsids of HEV particles are individually covered by lipid membranes resembling those of exosomes, similar to enveloped viruses. Hepatitis E, caused by HEV, is an important infectious disease that is spreading worldwide. HEV infection can cause acute or fulminant hepatitis and can become chronic in immunocompromised hosts, including patients after organ transplantation. The HEV particles present in feces and bile are nonenveloped, while those in circulating blood and culture supernatants are covered with a cellular membrane, similar to enveloped viruses. Furthermore, these membrane-associated and -unassociated HEV particles can be propagated in cultured cells. The significance of our research is that the capsids of HEV particles are individually covered by a lipid membrane that resembles the membrane of exosomes, similar to enveloped viruses, and are released from infected cells via the exosomal pathway. These data will help to elucidate the entry mechanisms and receptors for HEV infection in the future. This is the first report to characterize the detailed morphological features of membrane-associated HEV particles.
[Mh] Termos MeSH primário: Proteínas do Capsídeo/metabolismo
Exossomos/virologia
Vírus da Hepatite E/metabolismo
Hepatite E/metabolismo
Liberação de Vírus/fisiologia
[Mh] Termos MeSH secundário: Anticorpos Monoclonais Murinos/farmacologia
Linhagem Celular
Exossomos/metabolismo
Anticorpos Anti-Hepatite/farmacologia
Seres Humanos
Liberação de Vírus/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal, Murine-Derived); 0 (Capsid Proteins); 0 (Hepatitis Antibodies)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170908
[St] Status:MEDLINE


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[PMID]:28814517
[Au] Autor:Kaushik N; Subramani C; Anang S; Muthumohan R; Shalimar; Nayak B; Ranjith-Kumar CT; Surjit M
[Ad] Endereço:Virology Laboratory, Vaccine and Infectious Disease Research Centre, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, India.
[Ti] Título:Zinc Salts Block Hepatitis E Virus Replication by Inhibiting the Activity of Viral RNA-Dependent RNA Polymerase.
[So] Source:J Virol;91(21), 2017 Nov 01.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hepatitis E virus (HEV) causes an acute, self-limiting hepatitis in healthy individuals and leads to chronic disease in immunocompromised individuals. HEV infection in pregnant women results in a more severe outcome, with the mortality rate going up to 30%. Though the virus usually causes sporadic infection, epidemics have been reported in developing and resource-starved countries. No specific antiviral exists against HEV. A combination of interferon and ribavirin therapy has been used to control the disease with some success. Zinc is an essential micronutrient that plays crucial roles in multiple cellular processes. Zinc salts are known to be effective in reducing infections caused by few viruses. Here, we investigated the effect of zinc salts on HEV replication. In a human hepatoma cell (Huh7) culture model, zinc salts inhibited the replication of genotype 1 (g-1) and g-3 HEV replicons and g-1 HEV infectious genomic RNA in a dose-dependent manner. Analysis of a replication-defective mutant of g-1 HEV genomic RNA under similar conditions ruled out the possibility of zinc salts acting on replication-independent processes. An ORF4-Huh7 cell line-based infection model of g-1 HEV further confirmed the above observations. Zinc salts did not show any effect on the entry of g-1 HEV into the host cell. Furthermore, our data reveal that zinc salts directly inhibit the activity of viral RNA-dependent RNA polymerase (RdRp), leading to inhibition of viral replication. Taken together, these studies unravel the ability of zinc salts in inhibiting HEV replication, suggesting their possible therapeutic value in controlling HEV infection. Hepatitis E virus (HEV) is a public health concern in resource-starved countries due to frequent outbreaks. It is also emerging as a health concern in developed countries owing to its ability to cause acute and chronic infection in organ transplant and immunocompromised individuals. Although antivirals such as ribavirin have been used to treat HEV cases, there are known side effects and limitations of such therapy. Our discovery of the ability of zinc salts to block HEV replication by virtue of their ability to inhibit the activity of viral RdRp is important because these findings pave the way to test the efficacy of zinc supplementation therapy in HEV-infected patients. Since zinc supplementation therapy is known to be safe in healthy individuals and since high-dose zinc is used in the treatment of Wilson's disease, it may be possible to control HEV-associated health problems following a similar treatment regimen.
[Mh] Termos MeSH primário: Antivirais/farmacologia
Vírus da Hepatite E/efeitos dos fármacos
Hepatite E/tratamento farmacológico
RNA Replicase/antagonistas & inibidores
Replicação Viral/efeitos dos fármacos
Compostos de Zinco/farmacologia
[Mh] Termos MeSH secundário: Carcinoma Hepatocelular/enzimologia
Carcinoma Hepatocelular/patologia
Carcinoma Hepatocelular/virologia
Hepatite E/virologia
Vírus da Hepatite E/enzimologia
Vírus da Hepatite E/genética
Seres Humanos
Neoplasias Hepáticas/enzimologia
Neoplasias Hepáticas/patologia
Neoplasias Hepáticas/virologia
RNA Viral/genética
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (RNA, Viral); 0 (Zinc Compounds); EC 2.7.7.48 (RNA Replicase)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170818
[St] Status:MEDLINE



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