Base de dados : MEDLINE
Pesquisa : B04.820.087.565 [Categoria DeCS]
Referências encontradas : 59 [refinar]
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[PMID]:27512070
[Au] Autor:Surtees R; Dowall SD; Shaw A; Armstrong S; Hewson R; Carroll MW; Mankouri J; Edwards TA; Hiscox JA; Barr JN
[Ad] Endereço:Virology & Pathogenesis, Public Health England, Porton Down, Salisbury, United Kingdom School of Molecular and Cellular Biology, Faculty of Biological Sciences, and Astbury Centre for Molecular and Structural Biology, University of Leeds, Leeds, United Kingdom.
[Ti] Título:Heat Shock Protein 70 Family Members Interact with Crimean-Congo Hemorrhagic Fever Virus and Hazara Virus Nucleocapsid Proteins and Perform a Functional Role in the Nairovirus Replication Cycle.
[So] Source:J Virol;90(20):9305-16, 2016 Oct 15.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:UNLABELLED: The Nairovirus genus of the Bunyaviridae family contains serious human and animal pathogens classified within multiple serogroups and species. Of these serogroups, the Crimean-Congo hemorrhagic fever virus (CCHFV) serogroup comprises sole members CCHFV and Hazara virus (HAZV). CCHFV is an emerging zoonotic virus that causes often-fatal hemorrhagic fever in infected humans for which preventative or therapeutic strategies are not available. In contrast, HAZV is nonpathogenic to humans and thus represents an excellent model to study aspects of CCHFV biology under conditions of more-accessible biological containment. The three RNA segments that form the nairovirus genome are encapsidated by the viral nucleocapsid protein (N) to form ribonucleoprotein (RNP) complexes that are substrates for RNA synthesis and packaging into virus particles. We used quantitative proteomics to identify cellular interaction partners of CCHFV N and identified robust interactions with cellular chaperones. These interactions were validated using immunological methods, and the specific interaction between native CCHFV N and cellular chaperones of the HSP70 family was confirmed during live CCHFV infection. Using infectious HAZV, we showed for the first time that the nairovirus N-HSP70 association was maintained within both infected cells and virus particles, where N is assembled as RNPs. Reduction of active HSP70 levels in cells by the use of small-molecule inhibitors significantly reduced HAZV titers, and a model for chaperone function in the context of high genetic variability is proposed. These results suggest that chaperones of the HSP70 family are required for nairovirus replication and thus represent a genetically stable cellular therapeutic target for preventing nairovirus-mediated disease. IMPORTANCE: Nairoviruses compose a group of human and animal viruses that are transmitted by ticks and associated with serious or fatal disease. One member is Crimean-Congo hemorrhagic fever virus (CCHFV), which is responsible for fatal human disease and is recognized as an emerging threat within Europe in response to climate change. No preventative or therapeutic strategies against nairovirus-mediated disease are currently available. Here we show that the N protein of CCHFV and the related Hazara virus interact with a cellular protein, HSP70, during both the intracellular and extracellular stages of the virus life cycle. The use of inhibitors that block HSP70 function reduces virus titers by up to 1,000-fold, suggesting that this interaction is important within the context of the nairovirus life cycle and may represent a potent target for antinairovirus therapies against which the virus cannot easily develop resistance.
[Mh] Termos MeSH primário: Proteínas de Choque Térmico HSP70/metabolismo
Vírus da Febre Hemorrágica da Crimeia-Congo/genética
Vírus da Febre Hemorrágica da Crimeia-Congo/metabolismo
Nairovirus/genética
Nairovirus/metabolismo
Proteínas do Nucleocapsídeo/metabolismo
Replicação Viral/genética
[Mh] Termos MeSH secundário: Células A549
Linhagem Celular
Linhagem Celular Tumoral
Mudança Climática
Europa (Continente)
Células HEK293
Febre Hemorrágica da Crimeia/metabolismo
Febre Hemorrágica da Crimeia/virologia
Seres Humanos
RNA/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HSP70 Heat-Shock Proteins); 0 (Nucleocapsid Proteins); 63231-63-0 (RNA)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170509
[Lr] Data última revisão:
170509
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160812
[St] Status:MEDLINE
[do] DOI:10.1128/JVI.00661-16


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[PMID]:27412597
[Au] Autor:Deaton MK; Dzimianski JV; Daczkowski CM; Whitney GK; Mank NJ; Parham MM; Bergeron E; Pegan SD
[Ad] Endereço:Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, Georgia, USA.
[Ti] Título:Biochemical and Structural Insights into the Preference of Nairoviral DeISGylases for Interferon-Stimulated Gene Product 15 Originating from Certain Species.
[So] Source:J Virol;90(18):8314-27, 2016 Sep 15.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:UNLABELLED: The regulation of the interferon type I (IFN-I) response has been shown to rely on posttranslational modification by ubiquitin (Ub) and Ub-like interferon-stimulated gene product 15 (ISG15) to stabilize, or activate, a variety of IFN-I signaling and downstream effector proteins. Unlike Ub, which is almost perfectly conserved among eukaryotes, ISG15 is highly divergent, even among mammals. Since zoonotic viruses rely on viral proteins to recognize, or cleave, ISG15 conjugates in order to evade, or suppress, innate immunity, the impact of ISG15 biodiversity on deISGylating proteases of the ovarian tumor family (vOTU) from nairoviruses was evaluated. The enzymatic activities of vOTUs originating from the Crimean-Congo hemorrhagic fever virus, Erve virus, and Nairobi sheep disease virus were tested against ISG15s from humans, mice, shrews, sheep, bats, and camels, which are mammalian species known to be infected by nairoviruses. This along with investigation of binding by isothermal titration calorimetry illustrated significant differences in the abilities of nairovirus deISGylases to accommodate certain species of ISG15. To investigate the molecular underpinnings of species preferences of these vOTUs, a structure was determined to 2.5 Å for a complex of Erve virus vOTU protease and a mouse ISG15 domain. This structure revealed the molecular basis of Erve virus vOTU's preference for ISG15 over Ub and the first structural insight into a nonhuman ISG15. This structure also revealed key interactions, or lack thereof, surrounding three amino acids that may drive a viral deISgylase to prefer an ISG15 from one species over that of another. IMPORTANCE: Viral ovarian tumor domain proteases (vOTUs) are one of the two principal classes of viral proteases observed to reverse posttranslational modification of host proteins by ubiquitin and interferon-stimulated gene product 15 (ISG15), subsequently facilitating downregulation of IFN-I signaling pathways. Unlike the case with ubiquitin, the amino acid sequences of ISG15s from various species are notably divergent. We illustrate that vOTUs have clear preferences for ISG15s from certain species. In addition, these observations are related to the molecular insights acquired via the first X-ray structure of the vOTU from the Erve nairovirus in complex with the first structurally resolved nonhuman ISG15. This information implicates certain amino acids that drive the preference of vOTUs for ISG15s from certain species.
[Mh] Termos MeSH primário: Nairovirus/enzimologia
Peptídeo Hidrolases/metabolismo
Ubiquitinas/metabolismo
[Mh] Termos MeSH secundário: Animais
Cristalografia por Raios X
Seres Humanos
Modelos Moleculares
Nairovirus/fisiologia
Peptídeo Hidrolases/química
Ligação Proteica
Conformação Proteica
Proteólise
Ubiquitinas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ubiquitins); EC 3.4.- (Peptide Hydrolases)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170508
[Lr] Data última revisão:
170508
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160715
[St] Status:MEDLINE
[do] DOI:10.1128/JVI.00975-16


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[PMID]:27294949
[Au] Autor:Kuhn JH; Wiley MR; Rodriguez SE; Bào Y; Prieto K; Travassos da Rosa AP; Guzman H; Savji N; Ladner JT; Tesh RB; Wada J; Jahrling PB; Bente DA; Palacios G
[Ad] Endereço:Integrated Research Facility at Fort Detrick, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD 21702, USA. kuhnjens@mail.nih.gov.
[Ti] Título:Genomic Characterization of the Genus Nairovirus (Family Bunyaviridae).
[So] Source:Viruses;8(6), 2016 Jun 10.
[Is] ISSN:1999-4915
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Nairovirus, one of five bunyaviral genera, includes seven species. Genomic sequence information is limited for members of the Dera Ghazi Khan, Hughes, Qalyub, Sakhalin, and Thiafora nairovirus species. We used next-generation sequencing and historical virus-culture samples to determine 14 complete and nine coding-complete nairoviral genome sequences to further characterize these species. Previously unsequenced viruses include Abu Mina, Clo Mor, Great Saltee, Hughes, Raza, Sakhalin, Soldado, and Tillamook viruses. In addition, we present genomic sequence information on additional isolates of previously sequenced Avalon, Dugbe, Sapphire II, and Zirqa viruses. Finally, we identify Tunis virus, previously thought to be a phlebovirus, as an isolate of Abu Hammad virus. Phylogenetic analyses indicate the need for reassignment of Sapphire II virus to Dera Ghazi Khan nairovirus and reassignment of Hazara, Tofla, and Nairobi sheep disease viruses to novel species. We also propose new species for the Kasokero group (Kasokero, Leopards Hill, Yogue viruses), the Ketarah group (Gossas, Issyk-kul, Keterah/soft tick viruses) and the Burana group (Wenzhou tick virus, Huángpí tick virus 1, TÇŽchéng tick virus 1). Our analyses emphasize the sister relationship of nairoviruses and arenaviruses, and indicate that several nairo-like viruses (Shayáng spider virus 1, Xinzhou spider virus, Sanxiá water strider virus 1, South Bay virus, WÇ”hàn millipede virus 2) require establishment of novel genera in a larger nairovirus-arenavirus supergroup.
[Mh] Termos MeSH primário: Variação Genética
Genoma Viral
Nairovirus/classificação
Nairovirus/genética
Filogenia
[Mh] Termos MeSH secundário: Animais
Análise por Conglomerados
Sequenciamento de Nucleotídeos em Larga Escala
Nairovirus/isolamento & purificação
RNA Viral/genética
Análise de Sequência de DNA
Homologia de Sequência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Viral)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170913
[Lr] Data última revisão:
170913
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160614
[St] Status:MEDLINE


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[PMID]:26903607
[Au] Autor:Walker PJ; Widen SG; Wood TG; Guzman H; Tesh RB; Vasilakis N
[Ad] Endereço:CSIRO Health and Biosecurity, Australian Animal Health Laboratory, Geelong, Victoria, Australia; Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, Texas; Center for Biodefense and Emerging Infectious Diseases and Department of Pathology, Center for
[Ti] Título:A Global Genomic Characterization of Nairoviruses Identifies Nine Discrete Genogroups with Distinctive Structural Characteristics and Host-Vector Associations.
[So] Source:Am J Trop Med Hyg;94(5):1107-22, 2016 May 04.
[Is] ISSN:1476-1645
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Nairoviruses are primarily tick-borne bunyaviruses, some of which are known to cause mild-to-severe febrile illness in humans or livestock. We describe the genome sequences of 11 poorly characterized nairoviruses that have ecological associations with either birds (Farallon, Punta Salinas, Sapphire II, Zirqa, Avalon, Clo Mor, Taggert, and Abu Hammad viruses), rodents (Qalyub and Bandia viruses), or camels (Dera Ghazi Khan virus). Global phylogenetic analyses of proteins encoded in the L, M, and S RNA segments of these and 20 other available nairovirus genomes identified nine well-supported genogroups (Nairobi sheep disease, Thiafora, Sakhalin, Keterah, Qalyub, Kasokero, Dera Ghazi Khan, Hughes, and Tamdy). Genogroup-specific structural variations were evident, particularly in the M segment encoding a polyprotein from which virion envelope glycoproteins (Gn and Gc) are generated by proteolytic processing. Structural variations include the extension, abbreviation, or absence sequences encoding an O-glycosylated mucin-like protein in the N-terminal domain, distinctive patterns of conserved cysteine residues in the GP38-like domain, insertion of sequences encoding a double-membrane-spanning protein (NSm) between the Gn and Gc domains, and the presence of an alternative long open reading frame encoding a viroporin-like transmembrane protein (Gx). We also observed strong genogroup-specific associations with categories of hosts and tick vectors.
[Mh] Termos MeSH primário: Vetores Aracnídeos/fisiologia
Infecções por Bunyaviridae/veterinária
Genoma Viral
Nairovirus/genética
Doenças Transmitidas por Carrapatos/veterinária
Carrapatos/virologia
[Mh] Termos MeSH secundário: Animais
Infecções por Bunyaviridae/epidemiologia
Infecções por Bunyaviridae/virologia
Regulação Viral da Expressão Gênica
Especificidade de Hospedeiro
Nairovirus/classificação
Filogenia
Conformação Proteica
Doenças Transmitidas por Carrapatos/epidemiologia
Doenças Transmitidas por Carrapatos/virologia
Carrapatos/fisiologia
Proteínas Virais/química
Proteínas Virais/genética
Proteínas Virais/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Viral Proteins)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170509
[Lr] Data última revisão:
170509
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:160224
[St] Status:MEDLINE
[do] DOI:10.4269/ajtmh.15-0917


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[PMID]:26863911
[Au] Autor:Shimada S; Aoki K; Nabeshima T; Fuxun Y; Kurosaki Y; Shiogama K; Onouchi T; Sakaguchi M; Fuchigami T; Ono H; Nishi K; Posadas-Herrera G; Uchida L; Takamatsu Y; Yasuda J; Tsutsumi Y; Fujita H; Morita K; Hayasaka D
[Ad] Endereço:Department of Virology, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
[Ti] Título:Tofla virus: A newly identified Nairovirus of the Crimean-Congo hemorrhagic fever group isolated from ticks in Japan.
[So] Source:Sci Rep;6:20213, 2016 Feb 11.
[Is] ISSN:2045-2322
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Ixodid ticks transmit several important viral pathogens. We isolated a new virus (Tofla virus: TFLV) from Heamaphysalis flava and Heamaphysalis formsensis in Japan. The full-genome sequences revealed that TFLV belonged to the genus Nairovirus, family Bunyaviridae. Phylogenetic analyses and neutralization tests suggested that TFLV is closely related to the Hazara virus and that it is classified into the Crimean-Congo hemorrhagic fever group. TFLV caused lethal infection in IFNAR KO mice. The TFLV-infected mice exhibited a gastrointestinal disorder, and positron emission tomography-computed tomography images showed a significant uptake of (18)F-fluorodeoxyglucose in the intestinal tract. TFLV was able to infect and propagate in cultured cells of African green monkey-derived Vero E6 cells and human-derived SK-N-SH, T98-G and HEK-293 cells. Although TFLV infections in humans and animals are currently unknown, our findings may provide clues to understand the potential infectivity and to develop of pre-emptive countermeasures against this new tick-borne Nairovirus.
[Mh] Termos MeSH primário: Arbovirus/genética
Infecções por Bunyaviridae/virologia
Genoma Viral
Nairovirus/genética
Filogenia
Carrapatos/virologia
[Mh] Termos MeSH secundário: Animais
Arbovirus/classificação
Arbovirus/patogenicidade
Infecções por Bunyaviridae/mortalidade
Infecções por Bunyaviridae/patologia
Linhagem Celular Tumoral
Cercopithecus aethiops
Monitoramento Epidemiológico
Fluordesoxiglucose F18/metabolismo
Trato Gastrointestinal/patologia
Trato Gastrointestinal/virologia
Células HEK293
Seres Humanos
Japão
Camundongos
Camundongos Knockout
Nairovirus/classificação
Nairovirus/patogenicidade
Neuroglia/patologia
Neuroglia/virologia
Neurônios/patologia
Neurônios/virologia
Testes de Neutralização
Tomografia Computadorizada com Tomografia por Emissão de Pósitrons
Receptor de Interferon alfa e beta/deficiência
Receptor de Interferon alfa e beta/genética
Análise de Sequência de RNA
Análise de Sobrevida
Células Vero
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Ifnar1 protein, mouse); 0Z5B2CJX4D (Fluorodeoxyglucose F18); 156986-95-7 (Receptor, Interferon alpha-beta)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160212
[St] Status:MEDLINE
[do] DOI:10.1038/srep20213


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[PMID]:26677217
[Au] Autor:Hover S; King B; Hall B; Loundras EA; Taqi H; Daly J; Dallas M; Peers C; Schnettler E; McKimmie C; Kohl A; Barr JN; Mankouri J
[Ad] Endereço:From the School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT.
[Ti] Título:Modulation of Potassium Channels Inhibits Bunyavirus Infection.
[So] Source:J Biol Chem;291(7):3411-22, 2016 Feb 12.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Bunyaviruses are considered to be emerging pathogens facilitated by the segmented nature of their genome that allows reassortment between different species to generate novel viruses with altered pathogenicity. Bunyaviruses are transmitted via a diverse range of arthropod vectors, as well as rodents, and have established a global disease range with massive importance in healthcare, animal welfare, and economics. There are no vaccines or anti-viral therapies available to treat human bunyavirus infections and so development of new anti-viral strategies is urgently required. Bunyamwera virus (BUNV; genus Orthobunyavirus) is the model bunyavirus, sharing aspects of its molecular and cellular biology with all Bunyaviridae family members. Here, we show for the first time that BUNV activates and requires cellular potassium (K(+)) channels to infect cells. Time of addition assays using K(+) channel modulating agents demonstrated that K(+) channel function is critical to events shortly after virus entry but prior to viral RNA synthesis/replication. A similar K(+) channel dependence was identified for other bunyaviruses namely Schmallenberg virus (Orthobunyavirus) as well as the more distantly related Hazara virus (Nairovirus). Using a rational pharmacological screening regimen, two-pore domain K(+) channels (K2P) were identified as the K(+) channel family mediating BUNV K(+) channel dependence. As several K2P channel modulators are currently in clinical use, our work suggests they may represent a new and safe drug class for the treatment of potentially lethal bunyavirus disease.
[Mh] Termos MeSH primário: Antivirais/farmacologia
Vírus Bunyamwera/efeitos dos fármacos
Infecções por Bunyaviridae/tratamento farmacológico
Interações Hospedeiro-Patógeno/efeitos dos fármacos
Bloqueadores dos Canais de Potássio/farmacologia
Canais de Potássio de Domínios Poros em Tandem/antagonistas & inibidores
Integração Viral/efeitos dos fármacos
[Mh] Termos MeSH secundário: Aedes
Animais
Vírus Bunyamwera/crescimento & desenvolvimento
Vírus Bunyamwera/fisiologia
Infecções por Bunyaviridae/metabolismo
Infecções por Bunyaviridae/virologia
Linhagem Celular
Cercopithecus aethiops
Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos
Seres Humanos
Mesocricetus
Nairovirus/efeitos dos fármacos
Nairovirus/crescimento & desenvolvimento
Nairovirus/fisiologia
Orthobunyavirus/efeitos dos fármacos
Orthobunyavirus/crescimento & desenvolvimento
Orthobunyavirus/fisiologia
Canais de Potássio de Domínios Poros em Tandem/genética
Canais de Potássio de Domínios Poros em Tandem/metabolismo
Células Vero
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (KCNK1 protein, human); 0 (KCNK7 protein, human); 0 (KCNK9 protein, human); 0 (Potassium Channel Blockers); 0 (Potassium Channels, Tandem Pore Domain); 0 (potassium channel protein TREK-1)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151218
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M115.692673


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[PMID]:26455333
[Au] Autor:Papa A; Pappa S; Panayotova E; Papadopoulou E; Christova I
[Ad] Endereço:Aristotle University of Thessaloniki, Thessaloniki, Greece.
[Ti] Título:Molecular epidemiology of Crimean-Congo hemorrhagic fever in Bulgaria--An update.
[So] Source:J Med Virol;88(5):769-73, 2016 May.
[Is] ISSN:1096-9071
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Crimean-Congo hemorrhagic fever (CCHF) is endemic in Bulgaria. During 2013-2014, 11 confirmed CCHF cases have been reported in the country (seven in 2013 and four in 2014). The present study provides the CCHF molecular epidemiology in Bulgaria based on all currently available S, M, and L RNA segment nucleotide sequences spanning the years 1978-2014. A relatively low genetic difference (0-6%, the maximum seen in the M RNA segment) was seen among the CCHFV sequences suggesting that a slow evolving CCHFV strain belonging to "Europe 1" clade is present in Bulgaria. Although the virus emerged in new foci during the recent years, it is more active in the established endemic foci which seem to offer the most suitable ecosystem and environment. Understanding the CCHF epidemiology and virus evolution is the basis for public health programs and vaccine design.
[Mh] Termos MeSH primário: Doenças Endêmicas
Variação Genética
Vírus da Febre Hemorrágica da Crimeia-Congo/classificação
Vírus da Febre Hemorrágica da Crimeia-Congo/isolamento & purificação
Febre Hemorrágica da Crimeia/epidemiologia
Febre Hemorrágica da Crimeia/virologia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Bulgária/epidemiologia
Criança
Feminino
Genoma Viral
Vírus da Febre Hemorrágica da Crimeia-Congo/genética
Seres Humanos
Masculino
Meia-Idade
Epidemiologia Molecular
Nairovirus
Análise de Sequência de DNA
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Mês de entrada:1612
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151013
[St] Status:MEDLINE
[do] DOI:10.1002/jmv.24400


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[PMID]:26715309
[Au] Autor:Surtees R; Ariza A; Punch EK; Trinh CH; Dowall SD; Hewson R; Hiscox JA; Barr JN; Edwards TA
[Ad] Endereço:Public Health England, Porton Down, Salisbury, Wiltshire, SP4 0JG, UK. bs06ras@leeds.ac.uk.
[Ti] Título:The crystal structure of the Hazara virus nucleocapsid protein.
[So] Source:BMC Struct Biol;15:24, 2015 Dec 29.
[Is] ISSN:1472-6807
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Hazara virus (HAZV) is a member of the Bunyaviridae family of segmented negative stranded RNA viruses, and shares the same serogroup as Crimean-Congo haemorrhagic fever virus (CCHFV). CCHFV is responsible for fatal human disease with a mortality rate approaching 30 %, which has an increased recent incidence within southern Europe. There are no preventative or therapeutic treatments for CCHFV-mediated disease, and thus CCHFV is classified as a hazard group 4 pathogen. In contrast HAZV is not associated with serious human disease, although infection of interferon receptor knockout mice with either CCHFV or HAZV results in similar disease progression. To characterise further similarities between HAZV and CCHFV, and support the use of HAZV as a model for CCHFV infection, we investigated the structure of the HAZV nucleocapsid protein (N) and compared it to CCHFV N. N performs an essential role in the viral life cycle by encapsidating the viral RNA genome, and thus, N represents a potential therapeutic target. RESULTS: We present the purification, crystallisation and crystal structure of HAZV N at 2.7 Å resolution. HAZV N was expressed as an N-terminal glutathione S-transferase (GST) fusion protein then purified using glutathione affinity chromatography followed by ion-exchange chromatography. HAZV N crystallised in the P212121 space group with unit cell parameters a = 64.99, b = 76.10, and c = 449.28 Å. HAZV N consists of a globular domain formed mostly of alpha helices derived from both the N- and C-termini, and an arm domain comprising two long alpha helices. HAZV N has a similar overall structure to CCHFV N, with their globular domains superposing with an RMSD = 0.70 Å, over 368 alpha carbons that share 59 % sequence identity. Four HAZV N monomers crystallised in the asymmetric unit, and their head-to-tail assembly reveals a potential interaction site between monomers. CONCLUSIONS: The crystal structure of HAZV N reveals a close similarity to CCHFV N, supporting the use of HAZV as a model for CCHFV. Structural similarity between the N proteins should facilitate study of the CCHFV and HAZV replication cycles without the necessity of working under containment level 4 (CL-4) conditions.
[Mh] Termos MeSH primário: Nairovirus
Proteínas do Nucleocapsídeo/química
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Cristalografia por Raios X
Seres Humanos
Modelos Moleculares
Dados de Sequência Molecular
Proteínas do Nucleocapsídeo/genética
Proteínas do Nucleocapsídeo/isolamento & purificação
Proteínas do Nucleocapsídeo/metabolismo
Estrutura Secundária de Proteína
Eletricidade Estática
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Nucleocapsid Proteins)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151231
[St] Status:MEDLINE
[do] DOI:10.1186/s12900-015-0051-3


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[PMID]:26324724
[Au] Autor:Walker PJ; Widen SG; Firth C; Blasdell KR; Wood TG; Travassos da Rosa AP; Guzman H; Tesh RB; Vasilakis N
[Ad] Endereço:CSIRO Biosecurity, Australian Animal Health Laboratory, Geelong, Victoria, Australia; Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, Texas; Center for Biodefense and Emerging Infectious Diseases, Department of Pathology, The University of Texas M
[Ti] Título:Genomic Characterization of Yogue, Kasokero, Issyk-Kul, Keterah, Gossas, and Thiafora Viruses: Nairoviruses Naturally Infecting Bats, Shrews, and Ticks.
[So] Source:Am J Trop Med Hyg;93(5):1041-51, 2015 Nov.
[Is] ISSN:1476-1645
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The genus Nairovirus of arthropod-borne bunyaviruses includes the important emerging human pathogen, Crimean-Congo hemorrhagic fever virus (CCHFV), as well as Nairobi sheep disease virus and many other poorly described viruses isolated from mammals, birds, and ticks. Here, we report genome sequence analysis of six nairoviruses: Thiafora virus (TFAV) that was isolated from a shrew in Senegal; Yogue (YOGV), Kasokero (KKOV), and Gossas (GOSV) viruses isolated from bats in Senegal and Uganda; Issyk-Kul virus (IKV) isolated from bats in Kyrgyzstan; and Keterah virus (KTRV) isolated from ticks infesting a bat in Malaysia. The S, M, and L genome segments of each virus were found to encode proteins corresponding to the nucleoprotein, polyglycoprotein, and polymerase protein of CCHFV. However, as observed in Leopards Hill virus (LPHV) and Erve virus (ERVV), polyglycoproteins encoded in the M segment lack sequences encoding the double-membrane-spanning CCHFV NSm protein. Amino acid sequence identities, complement-fixation tests, and phylogenetic analysis indicated that these viruses cluster into three groups comprising KKOV, YOGV, and LPHV from bats of the suborder Yingochiroptera; KTRV, IKV, and GOSV from bats of the suborder Yangochiroptera; and TFAV and ERVV from shrews (Soricomorpha: Soricidae). This reflects clade-specific host and vector associations that extend across the genus.
[Mh] Termos MeSH primário: Infecções por Bunyaviridae/virologia
Quirópteros/virologia
Genoma Viral/genética
Nairovirus/genética
Musaranhos/virologia
Carrapatos/virologia
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Sequência de Bases
Infecções por Bunyaviridae/epidemiologia
Genômica
Seres Humanos
Quirguistão/epidemiologia
Malásia/epidemiologia
Nairovirus/classificação
Nairovirus/isolamento & purificação
Nucleoproteínas/genética
Filogenia
Senegal/epidemiologia
Alinhamento de Sequência
Análise de Sequência de DNA
Uganda/epidemiologia
Proteínas Virais/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Nucleoproteins); 0 (Viral Proteins)
[Em] Mês de entrada:1604
[Cu] Atualização por classe:161203
[Lr] Data última revisão:
161203
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:150902
[St] Status:MEDLINE
[do] DOI:10.4269/ajtmh.15-0344


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[PMID]:26246561
[Au] Autor:Wang W; Liu X; Wang X; Dong H; Ma C; Wang J; Liu B; Mao Y; Wang Y; Li T; Yang C; Guo Y
[Ad] Endereço:State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, People's Republic of China Institute of Molecular Science, Chemical Biology and Molecular Engineering Laboratory of Education Ministry, Shanxi University, Taiyuan, Shanxi, China.
[Ti] Título:Structural and Functional Diversity of Nairovirus-Encoded Nucleoproteins.
[So] Source:J Virol;89(23):11740-9, 2015 Dec.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:UNLABELLED: The nairoviruses include assorted tick-borne bunyaviruses that are emerging as causative agents of infectious diseases among humans and animals. As negative-sense single-stranded RNA (-ssRNA) viruses, nairoviruses encode nucleoprotein (NP) that encapsidates the genomic RNA and further forms ribonucleoprotein (RNP) complex with viral RNA-dependent RNA polymerase (RdRp). We previously revealed that the monomeric NP encoded by Crimean-Congo hemorrhagic fever virus (CCHFV) presents a racket-shaped structure and shows unusual DNA-specific endonuclease activity. To examine the structural and biological variation of nairovirus-encoded NPs, here, we systematically solved the crystal structures of NPs encoded by various nairoviruses, including Hazara virus (HAZV), Kupe virus (KUPV), and Erve virus (ERVEV). Combined with biochemical analysis, our results generate a clearer picture to aid in the understanding of the functional diversity of nairovirus-encoded NPs and the formation of nairovirus RNPs. IMPORTANCE: Nairoviruses comprise several tick-borne bunyaviruses that are emerging as causative agents of infectious diseases among humans and animals; however, little is known of the nairovirus genome assembly and transcription mechanisms. Based on the previous study of CCHFV NP reported by different research groups, we systematically investigate here the structural and functional diversity among three different nairoviruses. This work provides important information on nairovirus nucleoprotein function and the formation of RNPs.
[Mh] Termos MeSH primário: Variação Genética
Modelos Moleculares
Nairovirus/genética
Nucleoproteínas/genética
[Mh] Termos MeSH secundário: Cristalografia
Primers do DNA/genética
DNA Complementar/genética
Ensaio de Desvio de Mobilidade Eletroforética
Nucleoproteínas/química
Difração de Raios X
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (DNA Primers); 0 (DNA, Complementary); 0 (Nucleoproteins)
[Em] Mês de entrada:1603
[Cu] Atualização por classe:160601
[Lr] Data última revisão:
160601
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150807
[St] Status:MEDLINE
[do] DOI:10.1128/JVI.01680-15



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