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[PMID]:29438433
[Au] Autor:Oka T; Stoltzfus GT; Zhu C; Jung K; Wang Q; Saif LJ
[Ad] Endereço:Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, Wooster, OH, United States of America.
[Ti] Título:Attempts to grow human noroviruses, a sapovirus, and a bovine norovirus in vitro.
[So] Source:PLoS One;13(2):e0178157, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Noroviruses (NoVs) and Sapoviruses (SaVs) are enteric caliciviruses that have been detected in multiple mammalian species, including humans. Currently, efficient cell culture systems have been established only for murine NoVs and porcine SaV Cowden strain. Establishment of an efficient in vitro cell culture system for other NoVs and SaVs remains challenging; however, human NoV (HuNoV) replication in 3D cultured Caco-2 cells and a clone of Caco-2 cells, C2BBe1, human enteroids and in human B cells has been reported. In this study, we tested various cells and culture conditions to grow HuNoVs and a human SaV (HuSaV) to test the possibility of the propagation in different cells and culture conditions. We also attempted to grow a bovine NoV (BoNoV) in ex vivo organ cultures. We did not observe significant RNA level increases for HuSaV and BoNoV under our test conditions. HuNoV RNA levels increased to a maximum of ~600-fold in long-term Caco-2 cells that were cultured for 1-2 months in multi-well plates and inoculated with HuNoV-positive and bacteria-free human stool suspensions using serum-free medium supplemented with the bile acid, GCDCA. However, this positive result was inconsistent. Our results demonstrated that HuNoVs, BoNoV and HuSaV largely failed to grow in vitro under our test conditions. Our purpose is to share our findings with other researchers with the goal to develop efficient, reproducible simplified and cost-effective culture systems for human and animal NoVs and SaVs in the future.
[Mh] Termos MeSH primário: Norovirus/fisiologia
Sapovirus/fisiologia
[Mh] Termos MeSH secundário: Células CACO-2
Seres Humanos
Técnicas In Vitro
Reação em Cadeia da Polimerase/métodos
Replicação Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180214
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0178157


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[PMID]:28982120
[Au] Autor:Gonzales-Gustavson E; Timoneda N; Fernandez-Cassi X; Caballero A; Abril JF; Buti M; Rodriguez-Frias F; Girones R
[Ad] Endereço:Laboratory of Virus Contaminants of Water and Food, Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, Barcelona, Catalonia, Spain.
[Ti] Título:Identification of sapovirus GV.2, astrovirus VA3 and novel anelloviruses in serum from patients with acute hepatitis of unknown aetiology.
[So] Source:PLoS One;12(10):e0185911, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hepatitis is a general term meaning inflammation of the liver, which can be caused by a variety of viruses. However, a substantial number of cases remain with unknown aetiology. We analysed the serum of patients with clinical signs of hepatitis using a metagenomics approach to characterize their viral species composition. Four pools of patients with hepatitis without identified aetiological agents were evaluated. Additionally, one pool of patients with hepatitis E (HEV) and pools of healthy volunteers were included as controls. A high diversity of anelloviruses, including novel sequences, was found in pools from patients with hepatitis of unknown aetiology. Moreover, viruses recently associated with gastroenteritis as sapovirus GV.2 and astrovirus VA3 were also detected only in those pools. Besides, most of the HEV genome was recovered from the HEV pool. Finally, GB virus C and human endogenous retrovirus were found in the HEV and healthy pools. Our study provides an overview of the virome in serum from hepatitis patients suggesting a potential role of these viruses not previously described in cases of hepatitis. However, further epidemiologic studies are necessary to confirm their contribution to the development of hepatitis.
[Mh] Termos MeSH primário: Anelloviridae/isolamento & purificação
Hepatite Viral Humana/virologia
Mamastrovirus/isolamento & purificação
Sapovirus/isolamento & purificação
Viremia/sangue
[Mh] Termos MeSH secundário: Doença Aguda
Anelloviridae/classificação
Estudos de Casos e Controles
Hepatite Viral Humana/sangue
Sequenciamento de Nucleotídeos em Larga Escala
Seres Humanos
Mamastrovirus/classificação
Filogenia
Viremia/classificação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171006
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0185911


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[PMID]:28766060
[Au] Autor:Khamrin P; Kumthip K; Supadej K; Thongprachum A; Okitsu S; Hayakawa S; Ushijima H; Maneekarn N
[Ad] Endereço:Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
[Ti] Título:Noroviruses and sapoviruses associated with acute gastroenteritis in pediatric patients in Thailand: increased detection of recombinant norovirus GII.P16/GII.13 strains.
[So] Source:Arch Virol;162(11):3371-3380, 2017 Nov.
[Is] ISSN:1432-8798
[Cp] País de publicação:Austria
[La] Idioma:eng
[Ab] Resumo:Enteric caliciviruses, including noroviruses (NoVs) and sapoviruses (SaVs), are recognized as important etiologic agents of acute gastroenteritis (AGE) with considerable genetic diversity. In order to gain an overview of the molecular epidemiology of human NoVs and SaVs in children hospitalized with AGE in Chiang Mai, Thailand, a total of 889 fecal specimens were collected from 2012 to 2014 and screened for NoVs and SaVs. Out of 889 fecal specimens, 154 (17.3%) and 6 (0.7%) were positive for NoV GII isolates and SaV, respectively. Among the NoV GII, 10 different genotypes were identified with genotype GII.4 being predominant (103 strains), followed by GII.3 (17 strains), GII.13 (13 strains), GII.1 (7 strains), GII.6 (7 strains), GII.7 (2 strains), GII.17 (2 strains), and one each of GII.2, GII.15, and GII.21 genotypes. It was observed that four variants of NoV GII.4 (Den Haag 2006b, Apeldoorn 2007, New Orleans 2009, Sydney 2012) were detected from 2012 to 2014. Analysis of partial nucleotide sequences of RdRp and VP1 of the emerging NoV GII.13 strains (9 of 13 strains) revealed that they all were GII.P16/GII.13 recombinants. In addition, four different genotypes of SaV, GI.1 (2 strains), GII.1 (1 strain), GII.4 (2 strains), and GIV.1 (1 strain) were detected. The data revealed heterogeneity and a highly dynamic distribution of NoV and SaV genotypes circulating in children admitted to hospitals with AGE in Chiang Mai, Thailand, during the period of 2012 to 2014.
[Mh] Termos MeSH primário: Infecções por Caliciviridae/virologia
Gastroenterite/virologia
Norovirus/isolamento & purificação
Sapovirus/isolamento & purificação
[Mh] Termos MeSH secundário: Infecções por Caliciviridae/epidemiologia
Pré-Escolar
Fezes/virologia
Feminino
Gastroenterite/epidemiologia
Regulação Viral da Expressão Gênica/fisiologia
Seres Humanos
Lactente
Masculino
Norovirus/classificação
Norovirus/genética
Filogenia
Prevalência
RNA Viral
Sapovirus/classificação
Sapovirus/genética
Tailândia/epidemiologia
Proteínas Virais/genética
Proteínas Virais/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Viral); 0 (Viral Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171025
[Lr] Data última revisão:
171025
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170803
[St] Status:MEDLINE
[do] DOI:10.1007/s00705-017-3501-3


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[PMID]:28302145
[Au] Autor:Li J; Shen Q; Zhang W; Zhao T; Li Y; Jiang J; Yu X; Guo Z; Cui L; Hua X
[Ad] Endereço:School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, China.
[Ti] Título:Genomic organization and recombination analysis of a porcine sapovirus identified from a piglet with diarrhea in China.
[So] Source:Virol J;14(1):57, 2017 Mar 16.
[Is] ISSN:1743-422X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Sapovirus (SaV), a member of the family Caliciviridae, is an etiologic agent of gastroenteritis in humans and pigs. To date, both intra- and inter-genogroup recombinant strains have been reported in many countries except for China. Here, we report an intra-genogroup recombination of porcine SaV identified from a piglet with diarrhea of China. METHODS: A fecal sample from a 15-day-old piglet with diarrhea was collected from Shanghai, China. Common agents of gastroenteritis including porcine circovirus type 2, porcine rotavirus, porcine transmissible gastroenteritis virus, porcine SaV, porcine norovirus, and porcine epidemic diarrhea virus were detected by RT-PCR or PCR method. The complete genome of porcine SaV was then determined by RT-PCR method. Phylogenetic analyses based on the structural region and nonstructural (NS) region were carried out to group this SaV strain, and it was divided into different genotypes based on these two regions. Recombination analysis based on the genomic sequence was further performed to confirm this recombinant event and locate the breakpoint. RESULTS: All of the agents showed negative results except for SaV. Analysis of the complete genome sequence showed that this strain was 7387 nt long with two ORFs and belonged to SaV GIII. Phylogenetic analyses of the structural region (complete VP1 nucleotide sequences) grouped this strain into GIII-3, whereas of the nonstructural region (RdRp nucleotide sequences) grouped this strain into GIII-2. Recombination analysis based on the genomic sequence confirmed this recombinant event and identified two parental strains that were JJ259 (KT922089, GIII-2) and CH430 (KF204570, GIII-3). The breakpoint located at position 5139 nt of the genome (RdRp-capsid junction region). Etiologic analysis showed the fecal sample was negative with the common agents of gastroenteritis, except for porcine SaV, which suggested that this recombinant strain might lead to this piglet diarrhea. CONCLUSIONS: P2 strain was an intra-genogroup recombinant porcine SaV. To the best of our knowledge, this study would be the first report that intra-genogroup recombination of porcine SaV infection was identified in pig herd in China.
[Mh] Termos MeSH primário: Infecções por Caliciviridae/veterinária
Diarreia/veterinária
Ordem dos Genes
Recombinação Genética
Sapovirus/genética
Sapovirus/isolamento & purificação
Doenças dos Suínos/virologia
[Mh] Termos MeSH secundário: Animais
Animais Recém-Nascidos
Infecções por Caliciviridae/virologia
China
Diarreia/virologia
Filogenia
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Análise de Sequência de DNA
Suínos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170823
[Lr] Data última revisão:
170823
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170318
[St] Status:MEDLINE
[do] DOI:10.1186/s12985-017-0729-1


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[PMID]:28177797
[Au] Autor:Bergallo M; Galliano I; Montanari P; Brusin MR; Finotti S; Paderi G; Gabiano C
[Ad] Endereço:a Department of Public Health and Pediatric Sciences, University of Turin, Medical School, 10136 Turin, Italy.
[Ti] Título:Development of a quantitative real-time PCR assay for sapovirus in children under 5-years-old in Regina Margherita Hospital of Turin, Italy.
[So] Source:Can J Microbiol;63(4):296-302, 2017 Apr.
[Is] ISSN:1480-3275
[Cp] País de publicação:Canada
[La] Idioma:eng
[Ab] Resumo:Gastroenteritis is a common disease in children. It is characterized by diarrhea, vomiting, abdominal pain, and fever. Sapovirus (SaV) is a causative agent of acute gastroenteritis, but it causes milder illness than do rotavirus and norovirus. There is high variability in the analytical performance of quantitative PCR-based assays among clinical laboratories. This study developed a reverse transcription real-time PCR method to detect SaV in fecal specimens collected from children under 5-years-old with acute gastroenteritis. Of 137 episodes of acute gastroenteritis, 15 (10.9%) were associated with SaV genomic detection, with a median viral load of 6.6(log ) ± 7.1(log ) genomes/mg fecal specimens. There was a significant difference in detection rate between males and females (9.48% (13/15) vs. 1.46% (2/15), p = 0.0232). Among the 15 SaV-positive cases, 6 were also positive for rotavirus. Viral RNA recovery rate ranged from 46% to 77% in the manual RNAzol protocol and from 31% to 90% in the automated Maxwell protocol. We also studied whether human genomic DNA influences the sensitivity of the assay: its presence caused a decrease in PCR sensitivity. The development of a laboratory-designed real-time PCR TaqMan assay for quantitative detection of SaV and the optimization and standardization of this assay, using stools of children with acute gastroenteritis, are described.
[Mh] Termos MeSH primário: Gastroenterite/virologia
Reação em Cadeia da Polimerase em Tempo Real/métodos
Sapovirus/isolamento & purificação
[Mh] Termos MeSH secundário: Pré-Escolar
Fezes/virologia
Feminino
Seres Humanos
Lactente
Recém-Nascido
Masculino
RNA Viral/genética
Carga Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Viral)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170601
[Lr] Data última revisão:
170601
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170209
[St] Status:MEDLINE
[do] DOI:10.1139/cjm-2016-0482


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[PMID]:28046108
[Au] Autor:Grant LR; O'Brien KL; Weatherholtz RC; Reid R; Goklish N; Santosham M; Parashar U; Vinjé J
[Ad] Endereço:Center for American Indian Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
[Ti] Título:Norovirus and Sapovirus Epidemiology and Strain Characteristics among Navajo and Apache Infants.
[So] Source:PLoS One;12(1):e0169491, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Norovirus and sapovirus are important causes of acute gastroenteritis (AGE) among American Indian infants. We investigated the prevalence and molecular epidemiology of norovirus and sapovirus in American Indian infants who have historically experienced a high burden of AGE compared to other US populations. Stool samples were collected from 241 children with AGE (cases) and from 343 infants without AGE (controls) ≤9 months of age from 2002-2004. Cases experienced forceful vomiting and/or 3 or more watery or looser-than-normal stools in 24 hours. Stools were tested by real-time RT-PCR for norovirus GI, GII and GIV and sapovirus GI, GII, GIV and GV. Positive samples were genotyped after sequencing conventional RT-PCR products. Norovirus was identified in 76 (31.5%) of the cases and 70 (20.4%) of the controls (p<0.001). GII.3 and GII.4 Farmington Hills were the most frequently identified genotypes in 14.5% and 30.3% of cases and 17.1% and 27.1% of controls, respectively. Sapovirus GI and GII genotypes were identified in 8 (3.3%) of cases and 8 (2.3%) of controls and a single GIV virus was detected in a control. The same norovirus and sapovirus genotypes were circulating in the general U.S. population in the same time period. The high detection rate of norovirus in healthy controls suggests significant asymptomatic transmission in young infants in these communities.
[Mh] Termos MeSH primário: Infecções por Caliciviridae/etnologia
Diarreia/etnologia
Gastroenterite/etnologia
Índios Norte-Americanos
Norovirus/genética
Sapovirus/genética
[Mh] Termos MeSH secundário: Infecções por Caliciviridae/virologia
Estudos de Casos e Controles
Diarreia/virologia
Fezes/virologia
Gastroenterite/virologia
Variação Genética
Genótipo
Seres Humanos
Lactente
Recém-Nascido
Epidemiologia Molecular
Filogenia
Prevalência
Reação em Cadeia da Polimerase em Tempo Real
Estados Unidos/epidemiologia
Vômito
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170821
[Lr] Data última revisão:
170821
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170104
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0169491


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[PMID]:28040514
[Au] Autor:Bennett S; Gunson RN
[Ad] Endereço:West of Scotland Specialist Virology Centre, United Kingdom. Electronic address: susan.bennett@ggc.scot.nhs.uk.
[Ti] Título:The development of a multiplex real-time RT-PCR for the detection of adenovirus, astrovirus, rotavirus and sapovirus from stool samples.
[So] Source:J Virol Methods;242:30-34, 2017 Apr.
[Is] ISSN:1879-0984
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Viral gastroenteritis is a major health problem with significant morbidity and economic consequences. Viral gastroenteritis is caused by a number of viruses, including norovirus, rotavirus, adenovirus, astrovirus, and sapovirus. Conventional diagnosis is based on direct antigen detection and electron microscopy, however enzyme immunoassay's are insensitive and not available for all relevant pathogens, and electron microscope (EM) is no longer routinely carried out in most laboratories. Most laboratories now offer norovirus real-time PCR testing however the availability of other assays is variable. Commercial methods for the detection of inflectional intestinal disease (IID) are available but these can be expensive and are not commonly used. This paper describes the development of a single multiplex assay for the simultaneous detection of adenovirus, astrovirus, rotavirus and sapovirus from stool samples. The multiplex was evaluated by assessing endpoint sensitivity, specificity, panel of clinical samples, quality control (QC) panel and the robustness and reproducibility of the multiplex.
[Mh] Termos MeSH primário: Adenovírus Humanos/isolamento & purificação
Caliciviridae/isolamento & purificação
Fezes/virologia
Gastroenterite/diagnóstico
Mamastrovirus/isolamento & purificação
Reação em Cadeia da Polimerase Multiplex/métodos
Rotavirus/isolamento & purificação
[Mh] Termos MeSH secundário: Infecções por Adenovirus Humanos/diagnóstico
Infecções por Adenovirus Humanos/virologia
Adenovírus Humanos/genética
Caliciviridae/genética
Infecções por Caliciviridae/diagnóstico
Infecções por Caliciviridae/virologia
Primers do DNA
Sondas de DNA
Gastroenterite/virologia
Seres Humanos
Técnicas Imunoenzimáticas
Limite de Detecção
Mamastrovirus/genética
Norovirus/genética
Norovirus/isolamento & purificação
Reação em Cadeia da Polimerase em Tempo Real
Reprodutibilidade dos Testes
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Rotavirus/genética
Infecções por Rotavirus/diagnóstico
Infecções por Rotavirus/virologia
Sapovirus/genética
Sapovirus/isolamento & purificação
Sensibilidade e Especificidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA Primers); 0 (DNA Probes)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170102
[St] Status:MEDLINE


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[PMID]:27902397
[Au] Autor:Conley M; Emmott E; Orton R; Taylor D; Carneiro DG; Murata K; Goodfellow IG; Hansman GS; Bhella D
[Ad] Endereço:1​Medical Research Council - University of Glasgow Centre for Virus Research, Sir Michael Stoker Building, Garscube Campus, 464 Bearsden Road, Glasgow G61 1QH, UK.
[Ti] Título:Vesivirus 2117 capsids more closely resemble sapovirus and lagovirus particles than other known vesivirus structures.
[So] Source:J Gen Virol;98(1):68-76, 2017 Jan.
[Is] ISSN:1465-2099
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Vesivirus 2117 is an adventitious agent that, in 2009, was identified as a contaminant of Chinese hamster ovary cells propagated in bioreactors at a pharmaceutical manufacturing plant belonging to Genzyme. The consequent interruption in supply of Fabrazyme and Cerezyme (drugs used to treat Fabry and Gaucher diseases, respectively) caused significant economic losses. Vesivirus 2117 is a member of the Caliciviridae, a family of small icosahedral viruses encoding a positive-sense RNA genome. We have used cryo-electron microscopy and three-dimensional image reconstruction to calculate a structure of vesivirus 2117 virus-like particles as well as feline calicivirus and a chimeric sapovirus. We present a structural comparison of several members of the Caliciviridae, showing that the distal P domain of vesivirus 2117 is morphologically distinct from that seen in other known vesivirus structures. Furthermore, at intermediate resolutions, we found a high level of structural similarity between vesivirus 2117 and Caliciviridae from other genera: sapovirus and rabbit hemorrhagic disease virus. Phylogenetic analysis confirms vesivirus 2117 as a vesivirus closely related to canine vesiviruses. We postulate that morphological differences in virion structure seen between vesivirus clades may reflect differences in receptor usage.
[Mh] Termos MeSH primário: Capsídeo/ultraestrutura
Lagovirus/ultraestrutura
Sapovirus/ultraestrutura
Vesivirus/ultraestrutura
[Mh] Termos MeSH secundário: Animais
Cricetulus
Microscopia Crioeletrônica
Imagem Tridimensional
Filogenia
RNA Viral/genética
Análise de Sequência de DNA
Vesivirus/genética
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Viral)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161201
[St] Status:MEDLINE
[do] DOI:10.1099/jgv.0.000658


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[PMID]:27881647
[Au] Autor:Alfajaro MM; Choi JS; Kim DS; Seo JY; Kim JY; Park JG; Soliman M; Baek YB; Cho EH; Kwon J; Kwon HJ; Park SJ; Lee WS; Kang MI; Hosmillo M; Goodfellow I; Cho KO
[Ad] Endereço:Laboratory of Veterinary Pathology, College of Veterinary Medicine, Chonnam National University, Gwangju, Republic of Korea.
[Ti] Título:Activation of COX-2/PGE2 Promotes Sapovirus Replication via the Inhibition of Nitric Oxide Production.
[So] Source:J Virol;91(3), 2017 Feb 01.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Enteric caliciviruses in the genera Norovirus and Sapovirus are important pathogens that cause severe acute gastroenteritis in both humans and animals. Cyclooxygenases (COXs) and their final product, prostaglandin E (PGE ), are known to play important roles in the modulation of both the host response to infection and the replicative cycles of several viruses. However, the precise mechanism(s) by which the COX/PGE pathway regulates sapovirus replication remains largely unknown. In this study, infection with porcine sapovirus (PSaV) strain Cowden, the only cultivable virus within the genus Sapovirus, markedly increased COX-2 mRNA and protein levels at 24 and 36 h postinfection (hpi), with only a transient increase in COX-1 levels seen at 24 hpi. The treatment of cells with pharmacological inhibitors, such as nonsteroidal anti-inflammatory drugs or small interfering RNAs (siRNAs) against COX-1 and COX-2, significantly reduced PGE production, as well as PSaV replication. Expression of the viral proteins VPg and ProPol was associated with activation of the COX/PGE pathway. We observed that pharmacological inhibition of COX-2 dramatically increased NO production, causing a reduction in PSaV replication that could be restored by inhibition of nitric oxide synthase via the inhibitor N-nitro-l-methyl-arginine ester. This study identified a pivotal role for the COX/PGE pathway in the regulation of NO production during the sapovirus life cycle, providing new insights into the life cycle of this poorly characterized family of viruses. Our findings also reveal potential new targets for treatment of sapovirus infection. IMPORTANCE: Sapoviruses are among the major etiological agents of acute gastroenteritis in both humans and animals, but little is known about sapovirus host factor requirements. Here, using only cultivable porcine sapovirus (PSaV) strain Cowden, we demonstrate that PSaV induced the vitalization of the cyclooxygenase (COX) and prostaglandin E (PGE ) pathway. Targeting of COX-1/2 using nonsteroidal anti-inflammatory drugs (NSAIDs) such as the COX-1/2 inhibitor indomethacin and the COX-2-specific inhibitors NS-398 and celecoxib or siRNAs targeting COXs, inhibited PSaV replication. Expression of the viral proteins VPg and ProPol was associated with activation of the COX/PGE pathway. We further demonstrate that the production of PGE provides a protective effect against the antiviral effector mechanism of nitric oxide. Our findings uncover a new mechanism by which PSaV manipulates the host cell to provide an environment suitable for efficient viral growth, which in turn can be a new target for treatment of sapovirus infection.
[Mh] Termos MeSH primário: Infecções por Caliciviridae/metabolismo
Infecções por Caliciviridae/virologia
Ciclo-Oxigenase 2/metabolismo
Dinoprostona/metabolismo
Óxido Nítrico/biossíntese
Sapovirus/fisiologia
Replicação Viral
[Mh] Termos MeSH secundário: Animais
Ácidos e Sais Biliares/farmacologia
Infecções por Caliciviridae/genética
Linhagem Celular
Células Cultivadas
Ciclo-Oxigenase 1/genética
Ciclo-Oxigenase 1/metabolismo
Ciclo-Oxigenase 2/genética
Inibidores de Ciclo-Oxigenase 2/farmacologia
Expressão Gênica
Interferência de RNA
RNA Interferente Pequeno/genética
Transdução de Sinais/efeitos dos fármacos
Suínos
Replicação Viral/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bile Acids and Salts); 0 (Cyclooxygenase 2 Inhibitors); 0 (RNA, Small Interfering); 31C4KY9ESH (Nitric Oxide); EC 1.14.99.1 (Cyclooxygenase 1); EC 1.14.99.1 (Cyclooxygenase 2); K7Q1JQR04M (Dinoprostone)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170515
[Lr] Data última revisão:
170515
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161125
[St] Status:MEDLINE


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[PMID]:27756911
[Au] Autor:Ohba M; Oka T; Ando T; Arahata S; Ikegaya A; Takagi H; Ogo N; Zhu C; Owada K; Kawamori F; Wang Q; Saif LJ; Asai A
[Ad] Endereço:Center for Drug Discovery, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
[Ti] Título:Antiviral effect of theaflavins against caliciviruses.
[So] Source:J Antibiot (Tokyo);70(4):443-447, 2017 Apr.
[Is] ISSN:0021-8820
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Caliciviruses are contagious pathogens of humans and various animals. They are the most common cause of viral gastroenteritis in humans, and can cause lethal diseases in domestic animals such as cats, rabbits and immunocompromised mice. In this study, we conducted cytopathic effect-based screening of 2080 selected compounds from our in-house library to find antiviral compounds against three culturable caliciviruses: feline calicivirus, murine norovirus (MNV) and porcine sapovirus (PoSaV). We identified active six compounds, of which two compounds, both related to theaflavins, showed broad antiviral activities against all three caliciviruses; three compounds (abamectin, a mixture of avermectin B1a and B1b; avermectin B1a; and (-)-epigallocatechin gallate hydrate) were effective against PoSaV only; and a heterocyclic carboxamide derivative (BFTC) specifically inhibited MNV infectivity in cell cultures. Further studies of the antiviral mechanism and structure-activity relationship of theaflavins suggested the following: (1) theaflavins worked before the viral entry step; (2) the effect of theaflavins was time- and concentration-dependent; and (3) the hydroxyl groups of the benzocycloheptenone ring were probably important for the anti-calicivirus activity of theaflavins. Theaflavins could be used for the calicivirus research, and as potential disinfectants and antiviral reagents to prevent and control calicivirus infections in animals and humans.
[Mh] Termos MeSH primário: Antivirais/farmacologia
Biflavonoides/farmacologia
Caliciviridae/efeitos dos fármacos
Catequina/farmacologia
Flavinas/farmacologia
[Mh] Termos MeSH secundário: Animais
Infecções por Caliciviridae
Calicivirus Felino/efeitos dos fármacos
Catequina/análogos & derivados
Gatos
Efeito Citopatogênico Viral/efeitos dos fármacos
Avaliação Pré-Clínica de Medicamentos
Seres Humanos
Ivermectina/análogos & derivados
Ivermectina/farmacologia
Camundongos
Norovirus/efeitos dos fármacos
Estrutura Quaternária de Proteína
Sapovirus/efeitos dos fármacos
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Biflavonoids); 0 (Flavins); 1IA46M0D13 (theaflavin); 5U8924T11H (abamectin); 70288-86-7 (Ivermectin); 73989-17-0 (avermectin); 8R1V1STN48 (Catechin); BQM438CTEL (epigallocatechin gallate)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170504
[Lr] Data última revisão:
170504
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161021
[St] Status:MEDLINE
[do] DOI:10.1038/ja.2016.128



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