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1.
Elife ; 102021 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-33463525

RESUMO

Seasonal coronaviruses (OC43, 229E, NL63, and HKU1) are endemic to the human population, regularly infecting and reinfecting humans while typically causing asymptomatic to mild respiratory infections. It is not known to what extent reinfection by these viruses is due to waning immune memory or antigenic drift of the viruses. Here we address the influence of antigenic drift on immune evasion of seasonal coronaviruses. We provide evidence that at least two of these viruses, OC43 and 229E, are undergoing adaptive evolution in regions of the viral spike protein that are exposed to human humoral immunity. This suggests that reinfection may be due, in part, to positively selected genetic changes in these viruses that enable them to escape recognition by the immune system. It is possible that, as with seasonal influenza, these adaptive changes in antigenic regions of the virus would necessitate continual reformulation of a vaccine made against them.


Assuntos
Adaptação Fisiológica/genética , Antígenos Virais/genética , Evolução Biológica , Coronavirus/metabolismo , Estações do Ano , Simulação por Computador , Coronavirus/genética , Regulação Viral da Expressão Gênica , Humanos , Vírus da Influenza A/genética , Vírus do Sarampo/genética , Filogenia
3.
BMC Bioinformatics ; 21(Suppl 19): 573, 2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33349244

RESUMO

BACKGROUND: Coiled-coils are described as stable structural motifs, where two or more helices wind around each other. However, coiled-coils are associated with local mobility and intrinsic disorder. Intrinsically disordered regions in proteins are characterized by lack of stable secondary and tertiary structure under physiological conditions in vitro. They are increasingly recognized as important for protein function. However, characterizing their behaviour in solution and determining precisely the extent of disorder of a protein region remains challenging, both experimentally and computationally. RESULTS: In this work, we propose a computational framework to quantify the extent of disorder within a coiled-coil in solution and to help design substitutions modulating such disorder. Our method relies on the analysis of conformational ensembles generated by relatively short all-atom Molecular Dynamics (MD) simulations. We apply it to the phosphoprotein multimerisation domains (PMD) of Measles virus (MeV) and Nipah virus (NiV), both forming tetrameric left-handed coiled-coils. We show that our method can help quantify the extent of disorder of the C-terminus region of MeV and NiV PMDs from MD simulations of a few tens of nanoseconds, and without requiring an extensive exploration of the conformational space. Moreover, this study provided a conceptual framework for the rational design of substitutions aimed at modulating the stability of the coiled-coils. By assessing the impact of four substitutions known to destabilize coiled-coils, we derive a set of rules to control MeV PMD structural stability and cohesiveness. We therefore design two contrasting substitutions, one increasing the stability of the tetramer and the other increasing its flexibility. CONCLUSIONS: Our method can be considered as a platform to reason about how to design substitutions aimed at regulating flexibility and stability.


Assuntos
Biologia Computacional/métodos , Proteínas Virais/química , Sequência de Aminoácidos , Vírus do Sarampo/metabolismo , Simulação de Dinâmica Molecular , Vírus Nipah/metabolismo , Domínios Proteicos , Estabilidade Proteica , Estrutura Secundária de Proteína , Proteínas Virais/metabolismo
5.
Praxis (Bern 1994) ; 109(15): 1179-1181, 2020 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-33234038

RESUMO

CME Dermatology 22/Answers: Measles - Empidemiology and Clinical Manifestations Abstract. Measles is a highly contagious, acute and febrile illness that results from infection with measles virus. The World Health Organization (WHO) estimates a worldwide prevalence of ten million patients per year, leading to approximately 142 000 deaths (case fatality rate 1.4 %). The illness begins with fever, malaise and typically with at least one of the following signs: cough, coryza and/or conjunctivitis. Three to four days later, the characteristical rash appears. The primary clinical diagnosis needs to be confirmed by detection of specific IgM antibodies in serum or viral RNA by a throat swap. The management mainly consists of supportive therapy, a specific antiviral treatment does not exist. Therefore, prevention by widespread measles vaccination has absolute priority.


Assuntos
Dermatologia , Exantema , Sarampo , Exantema/etiologia , Humanos , Sarampo/diagnóstico , Sarampo/epidemiologia , Vírus do Sarampo , Vacinação
6.
Praxis (Bern 1994) ; 109(14): 1109-1116, 2020.
Artigo em Alemão | MEDLINE | ID: mdl-33108997

RESUMO

CME Dermatology 22: Measles - Empidemiology and Clinical Manifestations Abstract. Measles is a highly contagious, acute and febrile illness that results from infection with measles virus. The World Health Organization (WHO) estimates a worldwide prevalence of ten million patients per year, leading to approximately 142 000 deaths (case fatality rate 1.4 %). The illness begins with fever, malaise and typically with at least one of the following signs: cough, coryza and/or conjunctivitis. Three to four days later, the characteristical rash appears. The primary clinical diagnosis needs to be confirmed by detection of specific IgM antibodies in serum or viral RNA by a throat swap. The management mainly consists of supportive therapy, a specific antiviral treatment does not exist. Therefore, prevention by widespread measles vaccination has absolute priority.


Assuntos
Exantema , Sarampo , Dermatologia , Humanos , Sarampo/diagnóstico , Sarampo/epidemiologia , Vírus do Sarampo , Vacinação
9.
ACS Sens ; 5(9): 2747-2752, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32820626

RESUMO

With the current intense need for rapid and accurate detection of viruses due to COVID-19, we report on a platform technology that is well suited for this purpose, using intact measles virus for a demonstration. Cases of infection due to the measles virus are rapidly increasing, yet current diagnostic tools used to monitor for the virus rely on slow (>1 h) technologies. Here, we demonstrate the first biosensor capable of detecting the measles virus in minutes with no preprocessing steps. The key sensing element is an electrode coated with a self-assembled monolayer containing the measles antibody, immobilized through an N-heterocyclic carbene (NHC). The intact virus is detected by changes in resistance, giving a linear response to 10-100 µg/mL of the intact measles virus without the need to label or process the sample. The limit of detection is 6 µg/mL, which is at the lower limit of concentrations that can cause infections in primates. The NHC-based biosensors are shown to be superior to thiol-based systems, producing an approximately 10× larger response and significantly greater stability toward repeated measurements and long-term storage. This NHC-based biosensor thus represents an important development for both the rapid detection of the measles virus and as a platform technology for the detection of other biological targets of interest.


Assuntos
Anticorpos Imobilizados/imunologia , Benzimidazóis/química , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Vírus do Sarampo/isolamento & purificação , Anticorpos Imobilizados/química , Técnicas Eletroquímicas/instrumentação , Eletrodos , Ouro/química , Limite de Detecção , Vírus do Sarampo/imunologia
10.
Wiad Lek ; 73(4): 782-785, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32731716

RESUMO

OBJECTIVE: The aim: To study the clinical and epidemiological peculiarities of measles in adults according to the data of the Regional Clinical Infectious Disease Hospital in Ivano-Frankivsk, Ukraine. PATIENTS AND METHODS: Materials and methods: The article analyzes the epidemiological and clinical features of 113 cases of measles among adults who undergone inpatient treatment in 2017-2018. The diagnosis was confirmed by the detection of antiviral Ig M antibodies. Determination of the genotype of the virus was performed in Regional WHO Reference Laboratory in Luxembourg. RESULTS: Results: The genotype of the measles virus was MVs/Cambridge GBR/5.16 D8 is circulating through the region territory. In 98.3% of adult patients a typical clinical picture of moderate severity was observed. Measles was accompanied by complications such as acute bronchitis (23.9%), reactive hepatitis (13.3%), reactive pancreatitis (10.6%) andpneumonia (7.1%). CONCLUSION: Сonclusions: The following epidemiological peculiarities in adult patients with measles: young people are mostly ill, urban residents are not vaccinated, partly vaccinated or with an unknown vaccine status. There was a change in the genotype of the virus of measles circulating in the Ivano-Frankivsk region: in 2012 genotype MVs/ManchesterGBR/10.09D4was confirmed, now the genotype of the measles virus is MVS/ CambridgeGBR/5.16D8. In 98 (86.73%) patients was a typical clinical picture of the disease, of moderate severity. Among the complications of the disease were diagnosed: bronchitis and pneumonia (23.9% and 7.1% respectively), reactive hepatitis and reactive pancreatitis (13.3% and 10.6%).


Assuntos
Sarampo , Adulto , Anticorpos Antivirais , Surtos de Doenças , Genótipo , Humanos , Vírus do Sarampo , Ucrânia
13.
J Virol ; 94(17)2020 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-32581091

RESUMO

Measles virus (MeV) is a highly immunotropic and contagious pathogen that can even diminish preexisting antibodies and remains a major cause of childhood morbidity and mortality worldwide despite the availability of effective vaccines. MeV is one of the most extensively studied viruses with respect to the mechanisms of JAK-STAT antagonism. Of the three proteins translated from the MeV P gene, P and V are essential for inactivation of this pathway. However, the lack of data from direct analyses of the underlying interactions means that the detailed molecular mechanism of antagonism remains unresolved. Here, we prepared recombinant MeV V protein, which is responsible for human JAK-STAT antagonism, and a panel of variants, enabling the biophysical characterization of V protein, including direct V/STAT1 and V/STAT2 interaction assays. Unambiguous direct interactions between the host and viral factors, in the absence of other factors such as Jak1 or Tyk2, were observed, and the dissociation constants were quantified for the first time. Our data indicate that interactions between the C-terminal region of V and STAT2 is 1 order of magnitude stronger than that of the N-terminal region of V and STAT1. We also clarified that these interactions are completely independent of each other. Moreover, results of size exclusion chromatography demonstrated that addition of MeV-V displaces STAT2-core, a rigid region of STAT2 lacking the N- and C-terminal domains, from preformed complexes of STAT2-core/IRF-associated domain (IRF9). These results provide a novel model whereby MeV-V can not only inhibit the STAT2/IRF9 interaction but also disrupt preassembled interferon-stimulated gene factor 3.IMPORTANCE To evade host immunity, many pathogenic viruses inactivate host Janus kinase signal transducer and activator of transcription (STAT) signaling pathways using diverse strategies. Measles virus utilizes P and V proteins to counteract this signaling pathway. Data derived largely from cell-based assays have indicated several amino acid residues of P and V proteins as important. However, biophysical properties of V protein or its direct interaction with STAT molecules using purified proteins have not been studied. We have developed novel molecular tools enabling us to identify a novel molecular mechanism for immune evasion whereby V protein disrupts critical immune complexes, providing a clear strategy by which measles virus can suppress interferon-mediated antiviral gene expression.


Assuntos
Fator Gênico 3 Estimulado por Interferon, Subunidade gama/química , Vírus do Sarampo/metabolismo , Fosfoproteínas/química , Fator de Transcrição STAT2/química , Proteínas Virais/química , Sítios de Ligação , Expressão Gênica , Humanos , Evasão da Resposta Imune , Imunidade Inata , Fator Gênico 3 Estimulado por Interferon, Subunidade gama/genética , Fator Gênico 3 Estimulado por Interferon, Subunidade gama/metabolismo , Janus Quinases/metabolismo , Vírus do Sarampo/genética , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Ligação Proteica , Domínios Proteicos , Domínios e Motivos de Interação entre Proteínas , Fator de Transcrição STAT1/química , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT2/genética , Fator de Transcrição STAT2/metabolismo , Transdução de Sinais , Proteínas Virais/genética , Proteínas Virais/metabolismo , Dedos de Zinco
15.
Science ; 368(6497): 1367-1370, 2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32554594

RESUMO

Many infectious diseases are thought to have emerged in humans after the Neolithic revolution. Although it is broadly accepted that this also applies to measles, the exact date of emergence for this disease is controversial. We sequenced the genome of a 1912 measles virus and used selection-aware molecular clock modeling to determine the divergence date of measles virus and rinderpest virus. This divergence date represents the earliest possible date for the establishment of measles in human populations. Our analyses show that the measles virus potentially arose as early as the sixth century BCE, possibly coinciding with the rise of large cities.


Assuntos
Doenças Transmissíveis Emergentes/história , Evolução Molecular , Variação Genética , Vírus do Sarampo/genética , Sarampo/história , Cidades/história , Doenças Transmissíveis Emergentes/virologia , História Antiga , Humanos , Sarampo/virologia , Vírus da Peste Bovina/genética
16.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(6): 946-951, 2020 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-32564565

RESUMO

Objective: We isolated and identified the genotypes and molecular characteristics of the imported B3 measles virus (MeV) in Fujian province in 2018. Methods: Throat swab specimens were collected from clinically diagnosed measles patients and tested for viral RNA, using the real-time reverse transcription-polymerase chain reaction after the RNA extraction. Reverse transcription-polymerase chain reaction method was undertaken to amplify the 634 nucleotide acids of 3-terminal of the nucleoprotein gene. A phylogenetic tree was constructed and similarities in homology assessed. Results: We successfully isolated and obtained two measles virus strains and eighteen viral nucleic acid sequences. The Fujian strains were clustered within the same genotype group of WHO genotype B3 reference strains. Compared to the major circulating measles strain genotype B3 in the world, two Fujian strains MV18-41 and MV18-42 showed 100.0% nucleic acid homology to HongKong.CHN/35.18 strain which was isolated from Hong Kong in 2018. The remaining 16 Fujian strains showed the highest homology (99.9%) with the Mvs/Osaka.JPN/38.18/B3 strain isolated from Japan in 2018. Compared with other 23 WHO genotype reference strains, homology on both nucleotide and amino acid of the Fujian strain and the B1 genotype reference strain were the smallest, as 95.1%-95.4% and 95.3%, respectively. The differences of homology between the Fujian strain and H1 genotype reference strain were the largest, as 88.7%-89.0% and 87.3%, respectively. In addition, there were 13 mutation sites between the Fujian strain and the vaccine strain (Shanghai-191) at the 150 amino acid position of carboxy terminus on N protein, However, these sites did not cause functional changes in the protein region. Conclusions: In Fujian province, two strains of B3 genotype measles virus were obtained successfully, which were considered to be new genotype measles virus found in 2018. These findings showed it is necessary to strengthening the monitoring program on imported cases for better control and eliminate the measles virus.


Assuntos
Vírus do Sarampo/genética , Sarampo/virologia , China , Genótipo , Hong Kong , Humanos , Vírus do Sarampo/isolamento & purificação
17.
Arch Virol ; 165(8): 1895-1898, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32462283

RESUMO

We previously reported genotype D11 strains of measles virus that were first isolated from a measles outbreak associated with imported cases in Yunnan province of China by Zhang et al. (Emerg Infect Dis 16(6):943-7, 2010). Genotype D11 has been identified as the 24th genotype of the WHO reference strains. In this study, we sequenced the whole genome of a D11 strain. Phylogenetic analysis using the complete genome sequences of D11 and other reference strains showed that the D11 strain formed a distinct branch that was distant from the other genotypes and was most closely related to the reference strain D7. The M-F non-coding region (NCR) and the N450 coding region sequence (CDS) were found to be the most variable regions. This report provides basic genetic data on genotype D11 for further study of measles evolution and the support for measles elimination.


Assuntos
Genoma Viral/genética , Vírus do Sarampo/genética , China , Surtos de Doenças , Genótipo , Humanos , Sarampo/virologia , Filogenia , Análise de Sequência de DNA/métodos
19.
Rev. esp. quimioter ; 33(2): 116-121, abr. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-197713

RESUMO

OBJETIVOS: En 1998 la Región de Europa de la Organización Mundial de la Salud fijó el objetivo de eliminar el sarampión. En este estudio se analizó la prevalencia de la inmunidad frente al virus del sarampión en la población del área sanitaria de Santiago de Compostela a partir de los datos obtenidos entre 2008-2018. PACIENTES Y MÉTODOS: Se estudiaron 7.150 pacientes diferentes que se dividieron en grupos según su año de nacimiento: 2010-2017, 2000-2009, 1990-1999, 1980-1989, 1953-1979 y <1953. La determinación en suero de IgG frente al virus del sarampión se realizó mediante un inmunoensayo quimioluminiscente comercializado. RESULTADOS: Se observó un mínimo (76%) para las tasas de protección frente al virus del sarampión en los nacidos entre 1990-1999. Por grupo de edad se vio que en todos los grupos las mujeres presentaron un porcentaje superior de anticuerpos frente al sarampión. En un modelo de regresión logística con año de nacimiento y sexo se obtuvo una odds ratio para el año de nacimiento (p < 0,001) de 1,06 y para el sexo (p = 0,0013) de 0,82. CONCLUSIONES: Se observaron seroprevalencias inferiores a partir de la implantación de la vacuna, un cambio más acusado durante el periodo de implantación y desde el plan de vacunación para el sarampión del año 2000 en Galicia, las tasas de protección frente al virus del sarampión han ido aumentado en nuestra área. Aunque se observó una mayor proporción de mujeres protegidas frente a la de hombres, estas diferencias fueron escasas


OBJECTIVES: In 1998, the Europe Region of the World Health Organization set the goal of eliminating measles. In this study, the prevalence of immunity against measles virus in the population of the health area of Santiago de Compostela was analyzed based on data obtained between 2008-2018. METHODS: A total of 7,150 different patients were studied and divided into groups according to their year of birth: 2010-2017, 2000-2009, 1990-1999, 1980-1989, 1953-1979 and <1953. The serum determination of IgG against measles virus was performed using a commercialized chemiluminescent immunoassay. RESULTS: A minimum (76%) was observed for measles virus protection rates in those born between 1990-1999. By age group it was seen that in all groups the women presented a higher percentage of antibodies against measles. In a logistic regression model with year of birth and sex, an odds ratio of 1.06 (p < 0.001) was obtained for the year of birth and of 0.82 (p = 0.0013) for sex. CONCLUSIONS: It was observed lower seroprevalences from the implantation of the vaccine and a more pronounced change during the implantation period. From the vaccination plan for measles of the year 2000 in Galicia, the rates of protection against the virus of the measles have been increasing in our area. Although there is a greater proportion of women protected against men, these differences are small


Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Imunoglobulina G/sangue , Sarampo/imunologia , Vírus do Sarampo/imunologia , Fatores Etários , Estudos Transversais , Modelos Logísticos , Razão de Chances , Estudos Soroepidemiológicos , Espanha
20.
Rev. esp. quimioter ; 33(2): 122-129, abr. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-197714

RESUMO

OBJETIVOS: Describir la epidemiologia de las Enterobacterias portadoras de carbapenemasas (EPC) en un hospital de tercer nivel. MATERIAL Y MÉTODOS: Estudio observacional retrospectivo, se incluyeron todos los pacientes con muestra positiva para EPC atendidos en hospitalización o en el servicio de Urgencias, entre el 1 Enero de 2014 y el 31 de Diciembre de 2016. RESULTADOS: Se incluyeron 272 pacientes (316 muestras): 155 (57%) varones. Media de edad de 70,4 años (IC 95% 68,2-72,7). Media del índice de Charlson 3,6 (IC95% 3,4-3,8). En el 63,2% la adquisición fue nosocomial, en el 35,3% fue asociada a cuidados sanitarios (ACS). Presentaron infección el 55,1%, siendo la más frecuente la infección del tracto urinario (ITU) (58,7%). Las especies más frecuentes fueron Klebsiella pneumoniae (62,7%) y Enterobacter cloacae (10,1%). Los tipos de carbapenemasa más frecuente fueron OXA-48 (53,8%) y VIM (43%). La adquisición nosocomial se asoció con el género masculino, trasplante, inmunosupresión, ingreso en Unidad de Cuidados Intensivos (UCI) o Servicio Quirúrgico, tratamiento antibiótico previo, Enterobacter, VIM, infecciones respiratorias e intraabdominales. La adquisición ACS se asoció con mayor edad y comorbilidad, procedencia de residencia, sondaje vesical, mayor número de procedimientos ambulatorios, ingreso hospitalario previo, K. pneumoniae y E. coli, OXA-48, coproducción de betalactamasas de espectro extendido, ITU y sepsis. CONCLUSIONES: Los pacientes que adquieren la EPC en residencias presentan frecuentemente infección. Los pacientes con adquisición nosocomial se colonizan por EPC en la UCI, en relación a procedimientos invasivos y trasplante. Esta población presenta mayor mortalidad por desarrollar infecciones respiratorias por EPC


OBJECTIVE: To describe the epidemiology of Enterobacterales producing carbapenemases (EPC) in a tertiary hospital. MATERIAL AND METHODS: A retrospective observational study, all patients with a positive sample for EPC treated in hospitalization or in the Emergency Department were included, between January 1, 2014 and December 31, 2016. RESULTS: A total of 272 patients (316 samples) were included: 155 (57%) male. Mean age of 70.4 years (95% CI 68.2 -72.7). Mean Charlson index was 3.6 (95% CI 3.4-3.8). In 63.2% the acquisition was nosocomial, in 35.3% it was health-care associated (HA). 55.1% presented infection, the most frequent infection was urinary tract infection (UTI) (58.7%). The most frequent species were Klebsiella pneumoniae (62.7%) and Enterobacter cloacae (10.1%). The most frequent types of carbapenemase were OXA-48 (53.8%) and VIM (43%). The nosocomial acquisition was associated with the male gender, transplantation, immunosuppression, admission to the Intensive Care Unit (ICU) or surgical service, prior antibiotic treatment, Enterobacter, VIM, respiratory and intra-abdominal infections. The HA acquisition was associated with age and comorbidity, nursery home origin, bladder catheterization, greater number of outpatient procedures, previous hospital admission, K. pneumoniae and E. coli, OXA-48, coproduction of extended spectrum betalactamases, UTI and sepsis. CONCLUSIONS: Patients who acquire EPC in nursery homes frequently have an infection. Patients with nosocomial acquisition are colonized by EPC in the ICU, in relation to invasive procedures and transplantation. This population has a higher mortality due to developing respiratory infections by EPC


Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Imunoglobulina G/sangue , Sarampo/imunologia , Vírus do Sarampo/imunologia , Fatores Etários , Estudos Transversais , Modelos Logísticos , Razão de Chances , Estudos Soroepidemiológicos , Fatores Sexuais , Espanha
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