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1.
Viruses ; 11(7)2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31311112

RESUMO

Knowledge on haemostatic changes in humans infected with Ebola virus is limited due to safety concerns and access to patient samples. Ethical approval was obtained to collect plasma samples from patients in Sierra Leone infected with Ebola virus over time and samples were analysed for clotting time, fibrinogen, and D-dimer levels. Plasma from healthy volunteers was also collected by two methods to determine effect of centrifugation on test results as blood collected in Sierra Leone was not centrifuged. Collecting plasma without centrifugation only affected D-dimer values. Patients with Ebola virus disease had higher PT and APTT and D-dimer values than healthy humans with plasma collected in the same manner. Fibrinogen levels in patients with Ebola virus disease were normal or lower than values measured in healthy people. Clotting times and D-dimer levels were elevated during infection with Ebola virus but return to normal over time in patients that survived and therefore could be considered prognostic. Informative data can be obtained from plasma collected without centrifugation which could improve patient monitoring in hazardous environments.

2.
J Gen Virol ; 100(6): 911-912, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31021739

RESUMO

Members of the family Filoviridae produce variously shaped, often filamentous, enveloped virions containing linear non-segmented, negative-sense RNA genomes of 15-19 kb. Several filoviruses (e.g., Ebola virus) are pathogenic for humans and are highly virulent. Several filoviruses infect bats (e.g., Marburg virus), whereas the hosts of most other filoviruses are unknown. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on Filoviridae, which is available at www.ictv.global/report/filoviridae.

3.
Emerg Infect Dis ; 24(1)2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29261093

RESUMO

Ebola virus (EBOV) in body fluids poses risk for virus transmission. However, there are limited experimental data for such matrices on the disinfectant efficacy against EBOV. We evaluated the effectiveness of disinfectants against EBOV in blood on surfaces. Only 5% peracetic acid consistently reduced EBOV titers in dried blood to the assay limit of quantification.


Assuntos
Desinfetantes/farmacologia , Ebolavirus/efeitos dos fármacos , Clareadores/farmacologia , Células Cultivadas/virologia , Teste em Amostras de Sangue Seco , Humanos , Laboratórios , Ácido Peracético/farmacologia
4.
Viruses ; 9(5)2017 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-28492506

RESUMO

The mononegaviral family Filoviridae has eight members assigned to three genera and seven species. Until now, genus and species demarcation were based on arbitrarily chosen filovirus genome sequence divergence values (≈50% for genera, ≈30% for species) and arbitrarily chosen phenotypic virus or virion characteristics. Here we report filovirus genome sequence-based taxon demarcation criteria using the publicly accessible PAirwise Sequencing Comparison (PASC) tool of the US National Center for Biotechnology Information (Bethesda, MD, USA). Comparison of all available filovirus genomes in GenBank using PASC revealed optimal genus demarcation at the 55-58% sequence diversity threshold range for genera and at the 23-36% sequence diversity threshold range for species. Because these thresholds do not change the current official filovirus classification, these values are now implemented as filovirus taxon demarcation criteria that may solely be used for filovirus classification in case additional data are absent. A near-complete, coding-complete, or complete filovirus genome sequence will now be required to allow official classification of any novel "filovirus." Classification of filoviruses into existing taxa or determining the need for novel taxa is now straightforward and could even become automated using a presented algorithm/flowchart rooted in RefSeq (type) sequences.


Assuntos
Filoviridae/classificação , Filoviridae/genética , Filogenia , Algoritmos , Sequência de Bases , Bases de Dados de Ácidos Nucleicos , Ebolavirus/classificação , Ebolavirus/genética , Variação Genética , Genoma Viral , Marburgvirus/classificação , Marburgvirus/genética , Mononegavirais/classificação , Mononegavirais/genética , Análise de Sequência de DNA , Desenho de Programas de Computador , Especificidade da Espécie , Sequenciamento Completo do Genoma
5.
J Infect Dis ; 214(suppl 3): S268-S274, 2016 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-27471321

RESUMO

Ebola virus Makona (EBOV-Makona; from the 2013-2016 West Africa outbreak) shows decreased virulence in an immune-deficient mouse model, compared with a strain from 1976. Unlike other filoviruses tested, EBOV-Makona may be slightly more virulent by the aerosol route than by the injected route, as 2 mice died following aerosol exposure, compared with no mortality among mice that received intraperitoneal injection of equivalent or higher doses. Although most mice did not succumb to infection, the detection of an immunoglobulin G antibody response along with observed clinical signs suggest that the mice were infected but able to clear the infection and recover. We hypothesize that this may be due to the growth rates and kinetics of the virus, which appear slower than that for other filoviruses and consequently give more time for an immune response that results in clearance of the virus. In this instance, the immune-deficient mouse model is unlikely to be appropriate for testing medical countermeasures against this EBOV-Makona stock but may provide insight into pathogenesis and the immune response to virus.


Assuntos
Anticorpos Antivirais/sangue , Ebolavirus/patogenicidade , Doença pelo Vírus Ebola/virologia , Imunoglobulina G/sangue , Aerossóis , Animais , Modelos Animais de Doenças , Ebolavirus/crescimento & desenvolvimento , Ebolavirus/imunologia , Doença pelo Vírus Ebola/patologia , Humanos , Camundongos
6.
J Infect Dis ; 212 Suppl 2: S336-45, 2015 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-26209682

RESUMO

Ebola virus (EBOV) causes a highly infectious and lethal hemorrhagic fever in primates with high fatality rates during outbreaks and EBOV may be exploited as a potential biothreat pathogen. There is therefore a need to develop and license appropriate medical countermeasures against this virus. To determine whether the common marmoset (Callithrix jacchus) would be an appropriate model to assess vaccines or therapies against EBOV disease (EVD), initial susceptibility, lethality and pathogenesis studies were performed. Low doses of EBOV-Kikwit, between 4 and 27 times the 50% tissue culture infectious dose, were sufficient to cause a lethal, reproducible infection. Animals became febrile between days 5 and 6, maintaining a high fever before succumbing to EVD between 6 and 8 days after challenge. Typical signs of EVD were observed. Pathogenesis studies revealed that virus was isolated from the lungs of animals beginning on day 3 after challenge and from the liver, spleen and blood beginning on day 5. The most striking features were observed in animals that succumbed to infection, including high viral titers in all organs, increased levels of liver function enzymes and blood clotting times, decreased levels of platelets, multifocal moderate to severe hepatitis, and perivascular edema.


Assuntos
Callithrix/virologia , Ebolavirus/patogenicidade , Doença pelo Vírus Ebola/virologia , Doenças dos Macacos/virologia , Infecções Respiratórias/virologia , Animais , Callithrix/imunologia , Modelos Animais de Doenças , Vacinas contra Ebola/imunologia , Ebolavirus/imunologia , Feminino , Doença pelo Vírus Ebola/imunologia , Doença pelo Vírus Ebola/patologia , Fígado/imunologia , Fígado/patologia , Fígado/virologia , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Masculino , Doenças dos Macacos/imunologia , Doenças dos Macacos/patologia , Infecções Respiratórias/imunologia , Infecções Respiratórias/patologia , Baço/imunologia , Baço/patologia , Baço/virologia , Carga Viral/imunologia
7.
J Clin Microbiol ; 53(10): 3148-54, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26179307

RESUMO

Rapid inactivation of Ebola virus (EBOV) is crucial for high-throughput testing of clinical samples in low-resource, outbreak scenarios. The EBOV inactivation efficacy of Buffer AVL (Qiagen) was tested against marmoset serum (EBOV concentration of 1 × 10(8) 50% tissue culture infective dose per milliliter [TCID50 · ml(-1)]) and murine blood (EBOV concentration of 1 × 10(7) TCID50 · ml(-1)) at 4:1 vol/vol buffer/sample ratios. Posttreatment cell culture and enzyme-linked immunosorbent assay (ELISA) analysis indicated that treatment with Buffer AVL did not inactivate EBOV in 67% of samples, indicating that Buffer AVL, which is designed for RNA extraction and not virus inactivation, cannot be guaranteed to inactivate EBOV in diagnostic samples. Murine blood samples treated with ethanol (4:1 [vol/vol] ethanol/sample) or heat (60°C for 15 min) also showed no viral inactivation in 67% or 100% of samples, respectively. However, combined Buffer AVL and ethanol or Buffer AVL and heat treatments showed total viral inactivation in 100% of samples tested. The Buffer AVL plus ethanol and Buffer AVL plus heat treatments were also shown not to affect the extraction of PCR quality RNA from EBOV-spiked murine blood samples.


Assuntos
Tampões (Química) , Desinfetantes/farmacologia , Ebolavirus/efeitos dos fármacos , Ebolavirus/fisiologia , Etanol , Viabilidade Microbiana/efeitos dos fármacos , Inativação de Vírus/efeitos dos fármacos , Animais , Sangue/virologia , Callithrix , Camundongos
8.
Int J Exp Pathol ; 95(6): 378-91, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25477002

RESUMO

Glanders and melioidosis are caused by two distinct Burkholderia species and have generally been considered to have similar disease progression. While both of these pathogens are HHS/CDC Tier 1 agents, natural infection with both these pathogens is primarily through skin inoculation. The common marmoset (Callithrix jacchus) was used to compare disease following experimental subcutaneous challenge. Acute, lethal disease was observed in marmosets following challenge with between 26 and 1.2 × 10(8) cfu Burkholderia pseudomallei within 22-85 h. The reproducibility and progression of the disease were assessed following a challenge of 1 × 10(2) cfu of B. pseudomallei. Melioidosis was characterised by high levels of bacteraemia, focal microgranuloma progressing to non-necrotic multifocal solid lesions in the livers and spleens and multi-organ failure. Lethal disease was observed in 93% of animals challenged with Burkholderia mallei, occurring between 5 and 10.6 days. Following challenge with 1 × 10(2) cfu of B. mallei, glanders was characterised with lymphatic spread of the bacteria and non-necrotic, multifocal solid lesions progressing to a multifocal lesion with severe necrosis and pneumonia. The experimental results confirmed that the disease pathology and presentation is strikingly different between the two pathogens. The marmoset provides a model of the human syndrome for both diseases facilitating the development of medical countermeasures.


Assuntos
Burkholderia mallei , Burkholderia pseudomallei , Mormo/microbiologia , Mormo/patologia , Melioidose/microbiologia , Melioidose/patologia , Animais , Antígenos de Bactérias , Carga Bacteriana , Callithrix , Modelos Animais de Doenças , Feminino , Mormo/mortalidade , Injeções Subcutâneas , Masculino , Melioidose/mortalidade , Índice de Gravidade de Doença
9.
Genome Announc ; 2(6)2014 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-25414499

RESUMO

Ebola virus (EBOV) was discovered in 1976 around Yambuku, Zaire. A lack of nomenclature standards resulted in a variety of designations for each isolate, leading to confusion in the literature and databases. We sequenced the genome of isolate E718/ME/Ecran and unified the various designations under Ebola virus/H.sapiens-tc/COD/1976/Yambuku-Ecran.

10.
Virology ; 452-453: 324-33, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24461913

RESUMO

The resistance of adult immunocompetent mice to infection with ebolaviruses has led to the development of alternative small animal models that utilise immunodeficient mice, for example the interferon α/ß receptor knock-out mouse (IFNR(-/-)). IFNR(-/-) mice have been shown to be susceptible to infection with ebolaviruses by multiple routes but it is not known if this murine model is suitable for testing therapeutics that rely on the generation of an immune response for efficacy. We have tested recombinant adenovirus vectors for their ability to protect IFNR(-/-) mice from challenge with Ebola virus and have analysed the humoral response generated after immunisation. The recombinant vaccines elicited good levels of protection in the knock-out mouse and the antibody response in IFNR(-/-) mice was similar to that observed in vaccinated wild-type mice. These results indicate that the IFNR(-/-) mouse is a relevant small animal model for studying ebolavirus-specific therapeutics.


Assuntos
Adenoviridae/genética , Vacinas contra Ebola/imunologia , Ebolavirus/imunologia , Vetores Genéticos/genética , Doença pelo Vírus Ebola/prevenção & controle , Receptor de Interferon alfa e beta/deficiência , Proteínas do Envelope Viral/imunologia , Adenoviridae/metabolismo , Animais , Anticorpos Antivirais/imunologia , Modelos Animais de Doenças , Vacinas contra Ebola/administração & dosagem , Vacinas contra Ebola/genética , Ebolavirus/genética , Feminino , Vetores Genéticos/metabolismo , Doença pelo Vírus Ebola/genética , Doença pelo Vírus Ebola/imunologia , Doença pelo Vírus Ebola/virologia , Humanos , Masculino , Camundongos , Camundongos Knockout , Receptor de Interferon alfa e beta/genética , Vacinação , Proteínas do Envelope Viral/administração & dosagem , Proteínas do Envelope Viral/genética
11.
Antiviral Res ; 104: 153-5, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24462697

RESUMO

Filoviruses cause disease with high case fatality rates and are considered biological threat agents. Licensed post-exposure therapies that can be administered by the oral route are desired for safe and rapid distribution and uptake in the event of exposure or outbreaks. Favipiravir or T-705 has broad antiviral activity and has already undergone phase II and is undergoing phase III clinical trials for influenza. Here we report the first use of T-705 against Ebola virus. T-705 gave 100% protection against aerosol Ebola virus E718 infection; protection was shown in immune-deficient mice after 14 days of twice-daily dosing. T-705 was also shown to inhibit Ebola virus infection in cell culture. T-705 is likely to be licensed for use against influenza in the near future and could also be used with a new indication for filovirus infection.


Assuntos
Amidas/administração & dosagem , Antivirais/administração & dosagem , Ebolavirus/efeitos dos fármacos , Doença pelo Vírus Ebola/tratamento farmacológico , Doença pelo Vírus Ebola/virologia , Pirazinas/administração & dosagem , Administração Oral , Animais , Modelos Animais de Doenças , Doença pelo Vírus Ebola/mortalidade , Camundongos , Camundongos Knockout
12.
Arch Virol ; 159(4): 821-30, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24122154

RESUMO

The International Committee on Taxonomy of Viruses (ICTV) Filoviridae Study Group prepares proposals on the classification and nomenclature of filoviruses to reflect current knowledge or to correct disagreements with the International Code of Virus Classification and Nomenclature (ICVCN). In recent years, filovirus taxonomy has been corrected and updated, but parts of it remain controversial, and several topics remain to be debated. This article summarizes the decisions and discussion of the currently acting ICTV Filoviridae Study Group since its inauguration in January 2012.


Assuntos
Classificação/métodos , Filoviridae/classificação , Terminologia como Assunto , Humanos
13.
Arch Virol ; 159(5): 1229-37, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24190508

RESUMO

Specific alterations (mutations, deletions, insertions) of virus genomes are crucial for the functional characterization of their regulatory elements and their expression products, as well as a prerequisite for the creation of attenuated viruses that could serve as vaccine candidates. Virus genome tailoring can be performed either by using traditionally cloned genomes as starting materials, followed by site-directed mutagenesis, or by de novo synthesis of modified virus genomes or parts thereof. A systematic nomenclature for such recombinant viruses is necessary to set them apart from wild-type and laboratory-adapted viruses, and to improve communication and collaborations among researchers who may want to use recombinant viruses or create novel viruses based on them. A large group of filovirus experts has recently proposed nomenclatures for natural and laboratory animal-adapted filoviruses that aim to simplify the retrieval of sequence data from electronic databases. Here, this work is extended to include nomenclature for filoviruses obtained in the laboratory via reverse genetics systems. The previously developed template for natural filovirus genetic variant naming, (/)///-, is retained, but we propose to adapt the type of information added to each field for cDNA clone-derived filoviruses. For instance, the full-length designation of an Ebola virus Kikwit variant rescued from a plasmid developed at the US Centers for Disease Control and Prevention could be akin to "Ebola virus H.sapiens-rec/COD/1995/Kikwit-abc1" (with the suffix "rec" identifying the recombinant nature of the virus and "abc1" being a placeholder for any meaningful isolate designator). Such a full-length designation should be used in databases and the methods section of publications. Shortened designations (such as "EBOV H.sap/COD/95/Kik-abc1") and abbreviations (such as "EBOV/Kik-abc1") could be used in the remainder of the text, depending on how critical it is to convey information contained in the full-length name. "EBOV" would suffice if only one EBOV strain/variant/isolate is addressed.


Assuntos
Filoviridae/classificação , Filoviridae/genética , Vírus Reordenados/classificação , Vírus Reordenados/genética , Genoma Viral
14.
J Virol Methods ; 193(2): 565-71, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23748121

RESUMO

Two common methods of quantifying filovirus infectivity, a plaque assay and 50% cell culture infectious dose (TCID50) endpoint dilution assay, were compared. The two assays were performed side by side using the same virus stock sample to determine the correlation between the results of the two assays. The TCID50 assay appeared to be more sensitive but slightly more variable, and there was a tenfold difference in the numerical results of these methods of enumeration. The advantages and disadvantages of both assays are discussed. Both methods are useful and practicable in filovirus research, and this comparison will be hugely beneficial to the filovirus research community as it seeks to become more united. Further work in this area should be performed to ensure consistency in filovirus research.


Assuntos
Filoviridae/fisiologia , Viabilidade Microbiana , Carga Viral/métodos , Ensaio de Placa Viral/métodos , Animais , Cercopithecus aethiops , Filoviridae/crescimento & desenvolvimento , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Células Vero , Cultura de Vírus/métodos
15.
Int J Exp Pathol ; 94(2): 156-68, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23441639

RESUMO

Marburg virus causes a highly infectious and lethal haemorrhagic fever in primates and may be exploited as a potential biothreat pathogen. To combat the infection and threat of Marburg haemorrhagic fever, there is a need to develop and license appropriate medical countermeasures. To determine whether the common marmoset (Callithrix jacchus) would be an appropriate model to assess therapies against Marburg haemorrhagic fever, initial susceptibility, lethality and pathogenesis studies were performed. Low doses of virus, between 4 and 28 TCID50 , were sufficient to cause a lethal, reproducible infection. Animals became febrile between days 5 and 6, maintaining a high fever before succumbing to disease between 8 and 11 days postchallenge. Typical signs of Marburg virus infection were observed including haemorrhaging and a transient rash. In pathogenesis studies, virus was isolated from the animals' lungs from day 3 postchallenge and from the liver, spleen and blood from day 5 postchallenge. Early signs of histopathology were apparent in the kidney and liver from day 3. The most striking features were observed in animals exhibiting severe clinical signs, which included high viral titres in all organs, with the highest levels in the blood, increased levels in liver function enzymes and blood clotting times, decreased levels in platelets, multifocal moderate-to-severe hepatitis and perivascular oedema.


Assuntos
Callithrix , Modelos Animais de Doenças , Exposição por Inalação , Doença do Vírus de Marburg/patologia , Marburgvirus/patogenicidade , Doenças dos Macacos/patologia , Animais , Citocinas/metabolismo , Suscetibilidade a Doenças , Feminino , Humanos , Rim/patologia , Rim/virologia , Fígado/patologia , Fígado/virologia , Pulmão/patologia , Pulmão/virologia , Masculino , Doença do Vírus de Marburg/virologia , Marburgvirus/isolamento & purificação , Doenças dos Macacos/virologia , Baço/patologia , Baço/virologia
18.
Viruses ; 4(8): 1305-17, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23012627

RESUMO

Porton Down houses two separate sites capable of conducting high containment research on ACDP (Advisory Committee on Dangerous Pathogens) Hazard Group 4 agents: the Defence Science and Technology Laboratory (Dstl) and the Health Protection Agency (HPA), and filovirus research has been performed at Porton Down since the first Marburg virus disease outbreak in 1967. All work is conducted within primary containment either within cabinet lines (for in vitro work) or large rigid half-suit isolators (for in vivo work). There are extensive aerobiological facilities at high containment and the use of these facilities will be reported. Research at Dstl is primarily focused on assessing and quantifying the hazard, and testing the efficacy of medical countermeasures against filoviruses. Fundamental research directed to the study and understanding of the infectious and pathogenic nature of the filoviruses, particularly in aerosols, will be reported.


Assuntos
Contenção de Riscos Biológicos/instrumentação , Infecções por Filoviridae/prevenção & controle , Filoviridae , Substâncias Perigosas/normas , Laboratórios/organização & administração , Laboratórios/normas , Aerossóis/análise , Aerossóis/normas , Animais , Contenção de Riscos Biológicos/normas , Inglaterra , Ambiente Controlado , Filoviridae/patogenicidade , Filoviridae/fisiologia , Infecções por Filoviridae/virologia , Humanos
19.
J Med Microbiol ; 61(Pt 1): 8-15, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21852521

RESUMO

Normal immunocompetent mice are not susceptible to non-adapted filoviruses. There are therefore two strategies available to establish a murine model of filovirus infection: adaptation of the virus to the host or the use of genetically modified mice that are susceptible to the virus. A number of knockout (KO) strains of mice with defects in either their adaptive or innate immunity are susceptible to non-adapted filoviruses. In this study, A129 α/ß -/- interferon receptor-deficient KO mice, strain A129 IFN-α/ß -/-, were used to determine the lethality of a range of filoviruses, including Lake Victoria marburgvirus (MARV), Zaire ebolavirus (ZEBOV), Sudan ebolavirus (SEBOV), Reston ebolavirus (REBOV) and Côte d'Ivoire ebolavirus (CIEBOV), administered by using intraperitoneal (IP) or aerosol routes of infection. One hundred percent mortality was observed in all groups of KO mice that were administered with a range of challenge doses of MARV and ZEBOV by either IP or aerosol routes. Mean time to death for both routes was dose-dependent and ranged from 5.4 to 7.4 days in the IP injection challenge, and from 10.2 to 13 days in the aerosol challenge. The lethal dose (50 % tissue culture infective dose, TCID(50)) of ZEBOV for KO mice was <1 TCID(50) ml(-1) when administered by either the IP or aerosol route of infection; for MARV the lethal dose was <1 TCID(50) ml(-1) by the IP route of infection and <10 TCID(50) ml(-1) by the aerosol route. In contrast, there was no mortality after infection with SEBOV or REBOV by either IP or aerosol routes of infection; all the mice lost weight (~15 % loss of group mean body weight with SEBOV and ~7 % with REBOV) but recovered to their original weights by day 14 post-challenge. There was no mortality in mice administered with CIEBOV via the IP route of infection and no clinical signs of infection were observed. The progression of disease was faster following infection with ZEBOV than with MARV but ultimately both viruses caused widespread infection with high titres of the infectious viruses in multiple organs. Histopathological observations were consistent with other animal models and showed widespread organ damage. This study suggests that MARV and ZEBOV are more virulent when administered via the IP route rather than by aerosol infection, although both are highly virulent by either route. The KO mouse may provide a useful model to test potential antiviral therapeutics against wild-type filoviruses.


Assuntos
Aerossóis , Modelos Animais de Doenças , Infecções por Filoviridae/mortalidade , Infecções por Filoviridae/fisiopatologia , Filoviridae/patogenicidade , Receptor de Interferon alfa e beta/genética , Animais , Ebolavirus/patogenicidade , Feminino , Filoviridae/classificação , Infecções por Filoviridae/virologia , Doença pelo Vírus Ebola/mortalidade , Doença pelo Vírus Ebola/fisiopatologia , Doença pelo Vírus Ebola/virologia , Humanos , Injeções Intraperitoneais , Masculino , Doença do Vírus de Marburg/mortalidade , Doença do Vírus de Marburg/fisiopatologia , Doença do Vírus de Marburg/virologia , Marburgvirus/patogenicidade , Camundongos , Camundongos Knockout , Receptor de Interferon alfa e beta/deficiência , Virulência
20.
Science ; 334(6057): 821-4, 2011 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-22076380

RESUMO

The structure of BPSL1549, a protein of unknown function from Burkholderia pseudomallei, reveals a similarity to Escherichia coli cytotoxic necrotizing factor 1. We found that BPSL1549 acted as a potent cytotoxin against eukaryotic cells and was lethal when administered to mice. Expression levels of bpsl1549 correlate with conditions expected to promote or suppress pathogenicity. BPSL1549 promotes deamidation of glutamine-339 of the translation initiation factor eIF4A, abolishing its helicase activity and inhibiting translation. We propose to name BPSL1549 Burkholderia lethal factor 1.


Assuntos
Proteínas de Bactérias/química , Proteínas de Bactérias/toxicidade , Toxinas Bacterianas/química , Toxinas Bacterianas/toxicidade , Burkholderia pseudomallei/química , Burkholderia pseudomallei/patogenicidade , Fator de Iniciação 4A em Eucariotos/antagonistas & inibidores , Motivos de Aminoácidos , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Toxinas Bacterianas/genética , Toxinas Bacterianas/metabolismo , Domínio Catalítico , Linhagem Celular , Cristalografia por Raios X , Citotoxinas/química , Citotoxinas/genética , Citotoxinas/metabolismo , Citotoxinas/toxicidade , Proteínas de Escherichia coli/química , Fator de Iniciação 4A em Eucariotos/metabolismo , Glutamina/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Modelos Moleculares , Proteínas Mutantes/toxicidade , Iniciação Traducional da Cadeia Peptídica/efeitos dos fármacos , Ligação Proteica , Conformação Proteica , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína
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