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1.
Euro Surveill ; 25(3)2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31992389

RESUMO

Recognition of measles is crucial to prevent transmissions in the hospital settings. Little is known about the level of recognition of measles and possible causes of not recognising the disease by physicians in the post-vaccine era. We report on a measles outbreak in a paediatric hospital in Austria in January to February 2017 with strikingly high numbers of not recognised cases. The extent and course of the outbreak were assessed via retrospective case finding. Thirteen confirmed measles cases were identified, two with atypical clinical picture. Of eight cases with no known epidemiological link, only one was diagnosed immediately; four were recognised with delay and three only retrospectively. Eleven typical measles cases had four 'unrecognised visits' to the outpatient clinic and 28 on the ward. Two atypical cases had two 'unrecognised visits' to the outpatient clinic and 19 on the ward.Thirteen clinicians did not recognise typical measles (atypical cases not included). Twelve of 23 physicians involved had never encountered a patient with measles before. The direct and indirect costs related to the outbreak were calculated to be over EUR 80,000. Our findings suggest the need to establish regular training programmes about measles, including diagnostic pitfalls in paediatric hospitals.


Assuntos
Surtos de Doenças/estatística & dados numéricos , Vírus do Sarampo/genética , Vírus do Sarampo/imunologia , Sarampo/epidemiologia , Adolescente , Adulto , Áustria/epidemiologia , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Hospitais Pediátricos , Hospitais Universitários , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lactente , Masculino , Vírus do Sarampo/isolamento & purificação , RNA Viral/análise , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
3.
Eur J Epidemiol ; 34(10): 897-915, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31624970

RESUMO

Measles vaccination schedules and targets of herd immunity have been designed according to the paradigm that the vaccine is as protective as natural infection, and the virus has remained of a single serotype over many decades. As a result, ongoing measles resurgence is mostly attributed to gaps in immunization. Using official data, we investigated the correlation between the rate of vaccine coverage reported and aggregated at the national level, and the incidence of cases. We discussed the limits of this indicator considered in isolation. We provide a literature overview of measles vaccine efficacy and failures. We questioned whether measles strains could escape the vaccine. Immunization tools and strategies for measles control deserve to be optimized in the current context.


Assuntos
Surtos de Doenças/prevenção & controle , Vacina contra Sarampo/administração & dosagem , Vacina contra Sarampo/imunologia , Vírus do Sarampo/efeitos dos fármacos , Sarampo/prevenção & controle , Genótipo , Humanos , Vírus do Sarampo/genética , Vacinação
4.
Zhonghua Yu Fang Yi Xue Za Zhi ; 53(9): 929-933, 2019 Sep 06.
Artigo em Chinês | MEDLINE | ID: mdl-31474076

RESUMO

Objective: Analyze the genetic characteristic of Hemagglutinin(H) gene of measles viruses isolated in Henan Province in 2017. Methods: Swab samples collected from 7 lab confirmed measles cases, and we got the measles virus by Vero/Slam inoculation. Fragment of H genes were amplified by reverse transcription polymerase chain reaction(RT-PCR), then the PCR products were sequenced and analyzed. Results: The age of the 7 measles confirmed cases were between 1 and 50 years old, and all of them were males. All the 7 measles viruses were identified as H1a genotype, and the average distance of the nucleotides and the amino acids was 0.005, respectively. Compared with the Shanghai-191/China-vaccine, there were some changes in isolated virus, such as 240(th), 397(th) and 381(st) sites in the amino acid sequence. Conclusion: The measles genotype which isolated in Henan Province in 2017 was H1a. There were some difference from Shanghai-191/China-vaccine in the nucleotides sequence of H gene, which suggested that it's necessary to strengthen the monitor the variation of measles virus.


Assuntos
Hemaglutininas , Vírus do Sarampo , Sarampo/virologia , Adolescente , Adulto , Criança , Pré-Escolar , China , Genótipo , Hemaglutininas/genética , Humanos , Lactente , Masculino , Vacina contra Sarampo/genética , Vírus do Sarampo/genética , Pessoa de Meia-Idade , Filogenia , Adulto Jovem
6.
Int J Oncol ; 55(2): 347-358, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31268165

RESUMO

Virotherapy comprises a novel therapeutic approach to selectively eliminate cancer cells. Preclinical, as well as clinical data have demonstrated the efficacy of tumor­selective (oncolytic) viruses in hematological malignancies. In this study, we infected AML cell lines and primary AML cells from patients with measles vaccine virus either expressing GFP or armed with super cytosine deaminase, which converts the prodrug, 5­fluorocytosine, into the chemotherapeutic compound, 5­fluorouracil. Target cell density of the measles entry receptor, CD46, infection rates of targeted leukemic cells, tumor cell viability, and apoptotic rates were determined. We found that measles vaccine virus infected the leukemic blasts and profoundly diminished the number and viability of leukemic cells via the induction of apoptosis. The conversion of 5­fluorocytosine to 5­fluorouracil exerted a potent additive tumoricidal effect. This was also observed in cases when leukemic cells displayed only moderate susceptibility to the oncolytic virus and hence direct oncolysis. Taken together, in this study, we provide a first characterization of the combinatorial use of measles vaccine virus and 5­fluorouracil for treatment of AML. Our approach to site­specifically produce the active drug and combine this agent with the direct lytic effect of virotherapy may overcome present limitations and constitutes a feasible method with which to introduce 5­fluorouracil in the treatment of AML.


Assuntos
Fluoruracila/administração & dosagem , Leucemia Mieloide Aguda/terapia , Vírus do Sarampo/genética , Proteína Cofatora de Membrana/genética , Terapia Viral Oncolítica , Pró-Fármacos/administração & dosagem , Adulto , Idoso , Terapia Combinada , Feminino , Flucitosina/metabolismo , Fluoruracila/metabolismo , Seguimentos , Genes Transgênicos Suicidas , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Masculino , Proteína Cofatora de Membrana/metabolismo , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem
7.
MMWR Morb Mortal Wkly Rep ; 68(26): 587-591, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31269012

RESUMO

All six World Health Organization (WHO) regions have established measles elimination goals, and three regions have a rubella elimination goal. Each region has established a regional verification commission to monitor progress toward measles elimination, rubella elimination, or both, and to provide verification of elimination* (1,2). To verify elimination, high-quality case-based surveillance is essential, including laboratory confirmation of suspected cases and genotyping of viruses from confirmed cases to track transmission pathways. In 2000, WHO established the Global Measles and Rubella Laboratory Network (GMRLN) to provide high-quality laboratory support for surveillance for measles, rubella, and congenital rubella syndrome (3). GMRLN is the largest globally coordinated laboratory network, with 704 laboratories supporting surveillance in 191 countries (4). This report updates a previous report and describes the genetic characterization of measles and rubella viruses during 2016-2018 (5). The genetic diversity of measles viruses (MeVs) and rubella viruses (RuVs) has decreased globally following implementation of measles and rubella elimination strategies. Among 10,857 MeV sequences reported to the global Measles Nucleotide Surveillance (MeaNS) database during 2016-2018, the number of MeV genotypes detected in ongoing transmission decreased from six in 2016 to four in 2018. Among the 1,296 RuV sequences submitted to the global Rubella Nucleotide Surveillance (RubeNS) database during the same period, the number of RuV genotypes detected decreased from five in 2016 to two in 2018. To strengthen laboratory surveillance for measles and rubella elimination, specimens should be collected from all confirmed cases for genotyping, and sequences from all wild-type measles and rubella viruses should be submitted to MeaNS and RubeNS in a timely manner.


Assuntos
Erradicação de Doenças , Saúde Global/estatística & dados numéricos , Vírus do Sarampo/genética , Sarampo/prevenção & controle , Vigilância da População , Vírus da Rubéola/genética , Rubéola (Sarampo Alemão)/prevenção & controle , Bases de Dados Factuais , Genótipo , Objetivos , Humanos , Laboratórios , Sarampo/epidemiologia , Vírus do Sarampo/isolamento & purificação , Rubéola (Sarampo Alemão)/epidemiologia , Vírus da Rubéola/isolamento & purificação , Organização Mundial da Saúde
8.
PLoS One ; 14(6): e0218782, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31220172

RESUMO

Due to the Expanded Program on Immunization (EPI) and supplementary immunization activities (SIAs) in China, the incidence of measles in China has decreased extensively. The incidence reached its lowest levels in contemporary history in 2012 and 2017, with incidence rates of 4.6 and 4.3 per million population, respectively. However, more than 147,000 measles cases were reported from 2013 to 2016. Furthermore, the proportions of cases in infants < 8 months and adults have been increasing since 2013, representing a considerable challenge for measles elimination in China. A total of 14,868 measles viruses were isolated from confirmed measles cases from 2011 to 2017, of which 14,631 were identified as the predominant endemic genotype, H1; 87 were identified as genotype A viruses that were vaccine associated strains; and 150 were identified as non-H1 genotype viruses. The non-H1 genotype viruses included 62 D8 viruses, 70 D9 viruses, 3 D11 viruses, 14 B3 viruses, and 1 G3 virus, which were identified as imported or import-related viruses that caused sporadic cases or small outbreaks. Most of the transmission chains detected during the period 2011-2012 were interrupted and were followed by many new transmission chains of unknown origin that spread, causing a large measles resurgence in China during 2013-2016. After 4 years of measles resurgence and continuous implementation of the routine immunization program and SIAs, the population immunity reached a sufficiently high level to interrupt most of the transmission chains; only a few strains survived, which continued to be sporadically detected in China in 2017. In the present study, the results from the combined epidemiological and molecular virological data demonstrated the great progress towards measles elimination in China by the further analysis of circulation dynamics for the endemic H1 genotype measles virus from 2011 to 2017. And this study accumulated critical baseline data on circulating wild-type measles viruses in China and provides comprehensive information to the world. These comprehensive baseline data provide evidence to support measles elimination in the future, not only in China but also in other countries worldwide. In addition, the information will be very useful to other countries for tracing their sources of measles cases and for identifying transmission links, which can help prevent potential measles outbreaks.


Assuntos
Vírus do Sarampo/genética , Sarampo/epidemiologia , Sarampo/virologia , Adolescente , Adulto , Criança , Pré-Escolar , China/epidemiologia , Surtos de Doenças , Doenças Endêmicas , Feminino , Genótipo , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Sarampo/prevenção & controle , Vírus do Sarampo/classificação , Vírus do Sarampo/imunologia , Tipagem Molecular , Filogenia , Análise de Sequência de DNA , Vacinação , Adulto Jovem
9.
MMWR Morb Mortal Wkly Rep ; 68(17): 396-401, 2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31048675

RESUMO

In 2010, all 53 countries* in the World Health Organization (WHO) European Region (EUR) reconfirmed their commitment to eliminating measles and rubella and congenital rubella syndrome (1); this goal was included as a priority in the European Vaccine Action Plan 2015-2020 (2). The WHO-recommended elimination strategies in EUR include 1) achieving and maintaining ≥95% coverage with 2 doses of measles-containing vaccine (MCV) through routine immunization services; 2) providing measles and rubella vaccination opportunities, including supplementary immunization activities (SIAs), to populations susceptible to measles or rubella; 3) strengthening surveillance by conducting case investigations and confirming suspected cases and outbreaks with laboratory results; and 4) improving the availability and use of evidence for the benefits and risks associated with vaccination (3). This report updates a previous report (4) and describes progress toward measles elimination in EUR during 2009-2018. During 2009-2017, estimated regional coverage with the first MCV dose (MCV1) was 93%-95%, and coverage with the second dose (MCV2) increased from 73% to 90%. In 2017, 30 (57%) countries achieved ≥95% MCV1 coverage, and 15 (28%) achieved ≥95% coverage with both doses. During 2009-2018, >16 million persons were vaccinated during SIAs in 13 (24%) countries. Measles incidence declined to 5.8 per 1 million population in 2016, but increased to 89.5 in 2018, because of large outbreaks in several EUR countries. To achieve measles elimination in EUR, measures are needed to strengthen immunization programs by ensuring ≥95% 2-dose MCV coverage in every district of each country, offering supplemental measles vaccination to susceptible adults, maintaining high-quality surveillance for rapid case detection and confirmation, and ensuring effective outbreak preparedness and response.


Assuntos
Erradicação de Doenças , Surtos de Doenças/prevenção & controle , Sarampo/epidemiologia , Sarampo/prevenção & controle , Vigilância da População , Criança , Pré-Escolar , Europa (Continente)/epidemiologia , Genótipo , Humanos , Programas de Imunização , Esquemas de Imunização , Incidência , Lactente , Sarampo/virologia , Vacina contra Sarampo/administração & dosagem , Vírus do Sarampo/genética , Cobertura Vacinal/estatística & dados numéricos
10.
Mem Inst Oswaldo Cruz ; 114: e180545, 2019 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-30892375

RESUMO

Measles is a human infectious disease of global concern that is caused by the measles virus. In this study, we report the complete genome sequencing of one measles virus isolate, genotype D8, that was obtained directly from a urine sample in Boa Vista city, the capital of Roraima state in Brazil. Phylogenetic reconstruction grouped the genome described in this study with that of samples from Australia, South Korea, and Italy. To our knowledge, this is the first complete genome sequence of a wild-type measles virus reported from Latin America. Therefore, the present data strengthen the current knowledge on the molecular epidemiology of measles worldwide.


Assuntos
Vírus do Sarampo/genética , Sarampo/virologia , RNA Viral/genética , Brasil/epidemiologia , Surtos de Doenças , Genótipo , Humanos , Sarampo/epidemiologia , Filogenia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de RNA
11.
J Biosci ; 44(1)2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30837361

RESUMO

Measles virus is the causative agent of measles, a major cause of child mortality in developing countries. Two major proteins, coded by the viral genome, are nucleocapsid protein (N) and phosphoprotein (P). The N protein protects the viral genomic RNA and forms ribonucleoprotein complex (RNP) together with P protein. MeV-P protein recruits the large protein (L), i.e. viral RNA-depended RNA polymerase (RdRp), to ensure viral replication in host cell. Apoptogenic properties of N protein of Edmonston vaccine strain have been established in our lab previously. We investigated the role of MeV-P protein of Edmonston vaccine strain as modulator of apoptosis in cervical cancer cell line (HeLa) and found that MeV-P protein is anti-apoptotic and enhances cell proliferation. Measles virus is considered to be innately oncotropic virus. However, the anti-apoptotic property of MeV-P protein raises important concerns while adopting this virus as an anti-cancer therapeutic tool.


Assuntos
Vírus do Sarampo/genética , Proteínas do Nucleocapsídeo/genética , Fosfoproteínas/genética , Neoplasias do Colo do Útero/genética , Apoptose/genética , Movimento Celular/genética , Proliferação de Células/genética , RNA Polimerases Dirigidas por DNA/genética , Feminino , Genoma Viral/genética , Células HeLa , Humanos , Proteínas do Nucleocapsídeo/farmacologia , Terapia Viral Oncolítica , Fosfoproteínas/farmacologia , Retroviridae/genética , Ensaio Tumoral de Célula-Tronco , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/virologia , Vacinas Virais/genética , Vacinas Virais/imunologia
12.
Virus Res ; 265: 74-79, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30853585

RESUMO

Measles virus (MeV) is an immunosuppressive, extremely contagious RNA virus that remains a leading cause of death among children. MeV is dual-tropic: it replicates first in lymphatic tissue, causing immunosuppression, and then in epithelial cells of the upper airways, accounting for extremely efficient contagion. Efficient contagion is counter-intuitive because the enveloped MeV particles are large and relatively unstable. However, MeV particles can contain multiple genomes, which can code for proteins with different functional characteristics. These proteins can cooperate to promote virus spread in tissue culture, prompting the question of whether multi-genome MeV transmission may promote efficient MeV spread also in vivo. Consistent with this hypothesis, in well-differentiated primary human airway epithelia large genome populations spread rapidly through intercellular pores. In another line of research, it was shown that distinct lymphocytic-adapted and epithelial-adapted genome populations exist; cyclical adaptation studies indicate that suboptimal variants in one environment may constitute a low frequency reservoir for adaptation to the other environment. Altogether, these observations suggest that, in humans, MeV spread relies on en bloc genome transmission, and that genomic diversity is instrumental for rapid MeV dissemination within hosts.


Assuntos
Células Epiteliais/virologia , Genoma Viral , Vírus do Sarampo/genética , Sarampo/transmissão , Mucosa Respiratória/virologia , Células Cultivadas , Variação Genética , Humanos , Vírus do Sarampo/fisiologia , Receptores Virais/metabolismo , Sistema Respiratório , Vírion/metabolismo , Internalização do Vírus
14.
Braz J Infect Dis ; 23(1): 66-69, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30876879

RESUMO

Here we reported the outbreak of measles cases caused by the genotype D8 measles virus for the first time in Jiangsu province in China, which was possibly imported by a foreign student from Laos. Throat swab specimens were collected, and used to isolate virus. 634-bp fragment of the N gene and 1854-bp fragment of H gene were amplified by reverse transcription-PCR and sequenced, respectively. Phylogenetic results indicated that they belonged to genotype D8 measles virus. Further epidemiology investigation showed that the adults with D8 measles virus infection did not receive measles vaccine before having measles. In China, almost all D8 genotype MeV only infected those population without receiving measles vaccine immunization. Therefore, it is still necessary to implement the supplement activity of measles immunization target adult with immunity gap.


Assuntos
Doenças Transmissíveis Importadas/epidemiologia , Doenças Transmissíveis Importadas/virologia , Surtos de Doenças , Vírus do Sarampo/genética , Sarampo/epidemiologia , Sarampo/virologia , Adulto , China/epidemiologia , Feminino , Genótipo , Humanos , Vírus do Sarampo/isolamento & purificação , Filogenia
15.
Gene Ther ; 26(5): 151-164, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30718755

RESUMO

Induced pluripotent stem cells (iPSCs) provide a unique platform for individualized cell therapy approaches. Currently, episomal DNA, mRNA, and Sendai virus-based RNA reprogramming systems are widely used to generate iPSCs. However, they all rely on the use of multiple (three to six) components (vectors/plasmids/mRNAs) leading to the production of partially reprogrammed cells, reducing the efficiency of the systems. We produced a one-cycle measles virus (MV) vector by substituting the viral attachment protein gene with the green fluorescent protein (GFP) gene. Here, we present a highly efficient multi-transgene delivery system based on a vaccine strain of MV, a non-integrating RNA virus that has a long-standing safety record in humans. Introduction of the four reprogramming factors OCT4, SOX2, KLF4, and cMYC via a single, "one-cycle" MV vector efficiently reprogrammed human somatic cells into iPSCs, whereas MV vector genomes are rapidly eliminated in derived iPSCs. Our MV vector system offers a new reprogramming platform for genomic modification-free iPSCs amenable for clinical translation.


Assuntos
Técnicas de Reprogramação Celular/métodos , Reprogramação Celular , Técnicas de Transferência de Genes , Células-Tronco Pluripotentes Induzidas/citologia , Vírus do Sarampo/genética , Animais , Células Cultivadas , Vetores Genéticos , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Células Vero
16.
Int J Paleopathol ; 24: 266-278, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30743216

RESUMO

OBJECTIVE: Canine distemper virus (CDV), human measles virus (HMV), and rinderpest virus (RPV) of cattle are morbilliviruses that have caused devastating outbreaks for centuries. This paper seeks to reconstruct the evolutionary history of CDV. MATERIALS AND METHODS: An interdisciplinary approach is adopted, synthesizing paleopathological analysis of 96 Pre-Columbian dogs (750-1470 CE) from the Weyanoke Old Town, Virginia site, with historical reports, molecular analysis and morbilliviral epidemiology. RESULTS: Both measles (c.900CE) and rinderpest (c. 376 BCE) were first reported in Eurasia, while canine distemper was initially described in South America much later (1735 CE); there are no paleopathological indications of CDV in Weyanoke Old Town dogs. Molecularly, CDV is closely related to HMV, while viral codon usage indicates CDV may have previously infected humans; South American measles epidemics occurred prior to the emergence of canine distemper and would have facilitated HMV transmission and adaptation to dogs. CONCLUSIONS: The measles epidemics that decimated indigenous South American populations in the 1500-1700 s likely facilitated the establishment of CDV as a canine pathogen, which eventually spread to Europe and beyond. SIGNIFICANCE: Understanding the historical and environmental conditions that have driven morbilliviral evolution provides important insights into potential future threats of animal/human cross-species infections. LIMITATIONS: Interpreting historical disease descriptions is difficult and the archaeological specimens are limited. Molecular sequence data and codon usage analyses rely on modern viruses. SUGGESTIONS FOR FURTHER RESEARCH: Interdisciplinary approaches are increasingly needed to understand diseases of the past and present, as critical information and knowledge is scattered in different disciplines.


Assuntos
Vírus da Cinomose Canina/genética , Cinomose/epidemiologia , Morbillivirus/genética , Animais , Cinomose/história , Cinomose/patologia , Cinomose/virologia , Cães , Europa (Continente)/epidemiologia , História do Século XVI , História do Século XVII , História do Século XVIII , História Antiga , Humanos , Pesquisa Interdisciplinar , Vírus do Sarampo/genética , Paleopatologia , Filogenia , Vírus da Peste Bovina/genética , América do Sul/epidemiologia , Virginia/epidemiologia
17.
Structure ; 27(4): 660-668.e4, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30799076

RESUMO

Nipah virus is a highly lethal zoonotic pathogen found in Southeast Asia that has caused human encephalitis outbreaks with 40%-70% mortality. NiV encodes its own RNA-dependent RNA polymerase within the large protein, L. Efficient polymerase activity requires the phosphoprotein, P, which tethers L to its template, the viral nucleocapsid. P is a multifunctional protein with modular domains. The central P multimerization domain is composed of a long, tetrameric coiled coil. We investigated the importance of structural features found in this domain for polymerase function using a newly constructed NiV bicistronic minigenome assay. We identified a conserved basic patch and central kink in the coiled coil that are important for polymerase function, with R555 being absolutely essential. This basic patch and central kink are conserved in the related human pathogens measles and mumps viruses, suggesting that this mechanism may be conserved.


Assuntos
RNA Polimerases Dirigidas por DNA/química , Genoma Viral , Vírus Nipah/química , Fosfoproteínas/química , RNA Replicase/química , Proteínas Virais/química , Sequência de Aminoácidos , Sítios de Ligação , Clonagem Molecular , Sequência Conservada , Cristalografia por Raios X , RNA Polimerases Dirigidas por DNA/genética , RNA Polimerases Dirigidas por DNA/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Humanos , Vírus do Sarampo/química , Vírus do Sarampo/enzimologia , Vírus do Sarampo/genética , Modelos Moleculares , Vírus da Caxumba/química , Vírus da Caxumba/enzimologia , Vírus da Caxumba/genética , Vírus Nipah/enzimologia , Vírus Nipah/genética , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Ligação Proteica , Conformação Proteica em alfa-Hélice , Domínios e Motivos de Interação entre Proteínas , Multimerização Proteica , RNA Replicase/genética , RNA Replicase/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Proteínas Virais/genética , Proteínas Virais/metabolismo
18.
Viruses ; 11(1)2019 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-30621148

RESUMO

Recently, we found that the cytidine deaminase APOBEC3G (A3G) inhibits measles (MV) replication. Using a microarray, we identified differential regulation of several host genes upon ectopic expression of A3G. One of the up-regulated genes, the endoplasmic reticulum (ER) protein retention receptor KDELR2, reduced MV replication ~5 fold when it was over-expressed individually in Vero and CEM-SS T cells. Silencing of KDELR2 in A3G-expressing Vero cells abrogated the antiviral activity induced by A3G, confirming its role as an A3G-regulated antiviral host factor. Recognition of the KDEL (Lys-Asp-Glu-Leu) motif by KDEL receptors initiates the retrograde transport of soluble proteins that have escaped the ER and play an important role in ER quality control. Although KDELR2 over-expression reduced MV titers in cell cultures, we observed no interaction between KDELR2 and the MV hemagglutinin (H) protein. Instead, KDELR2 retained chaperones in the ER, which are required for the correct folding and transport of the MV envelope glycoproteins H and fusion protein (F) to the cell surface. Our data indicate that KDELR2 competes with MV envelope proteins for binding to calnexin and GRP78/Bip, and that this interaction limits the availability of the chaperones for MV proteins, causing the reduction of virus spread and titers.


Assuntos
Hemaglutininas Virais/metabolismo , Interações entre Hospedeiro e Microrganismos , Vírus do Sarampo/genética , Proteínas de Transporte Vesicular/metabolismo , Proteínas Virais de Fusão/metabolismo , Animais , Calnexina/metabolismo , Regulação da Expressão Gênica , Inativação Gênica , Células HEK293 , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Hemaglutininas Virais/genética , Humanos , Vírus do Sarampo/fisiologia , Células Vero , Proteínas de Transporte Vesicular/genética , Proteínas Virais de Fusão/genética , Carga Viral
19.
Cancer Immunol Immunother ; 68(4): 533-544, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30656384

RESUMO

Cancer immunotherapy is seeing an increasing focus on vaccination with tumor-associated antigens (TAAs). Human telomerase (hTERT) is a TAA expressed by most tumors to overcome telomere shortening. Tolerance to hTERT can be easily broken both naturally and experimentally and hTERT DNA vaccine candidates have been introduced in clinical trials. DNA prime/boost strategies have been widely developed to immunize efficiently against infectious diseases. We explored the use of a recombinant measles virus (MV) hTERT vector to boost DNA priming as recombinant live attenuated measles virus has an impressive safety and efficacy record. Here, we show that a MV-TERT vector can rapidly and strongly boost DNA hTERT priming in MV susceptible IFNAR/CD46 mouse models. The cellular immune responses were Th1 polarized. No humoral responses were elicited. The 4 kb hTERT transgene did not impact MV replication or induction of cell-mediated responses. These findings validate the MV-TERT vector to boost cell-mediated responses following DNA priming in humans.


Assuntos
Vacinas Anticâncer/imunologia , Epitopos de Linfócito T/imunologia , Vetores Genéticos , Imunidade Celular , Vírus do Sarampo , Linfócitos T/imunologia , Telomerase/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Vacinas Anticâncer/genética , Linhagem Celular , Citocinas/metabolismo , Citotoxicidade Imunológica , Vetores Genéticos/genética , Humanos , Imunização , Imunização Secundária , Vírus do Sarampo/genética , Camundongos , Camundongos Transgênicos , Telomerase/genética , Vacinas de DNA , Células Vero
20.
BMC Infect Dis ; 19(1): 90, 2019 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-30683064

RESUMO

BACKGROUND: Measles is one of the most infectious diseases with a high mortality rate worldwide. It is caused by the measles virus (MeV) which is a single stranded RNA virus with genetic diversity based on the nucleoprotein gene, including 24 genotypes. In Gabon, several outbreaks occurred in the past few years, especially in 2016 in Libreville and Oyem. A surveillance network of infectious diseases highlighted a measles outbreak which occurred in the south of Gabon from April to June 2017. METHODS: Clinical specimens of urine, blood, throat and nasal swabs were collected in the two main cities of the Haut-Ogooue province, Franceville and Moanda. Virological investigations based on real-time polymerase chain reaction for molecular diagnosis and conventional PCR for genotype identification were done. RESULTS: Specimens were collected from 139 suspected measles patients. A total of 46 (33.1%) children and adults were laboratory-confirmed cases among which 16 (34.8%) were unvaccinated, 16 (34.8%) had received one dose, and 11 (23.9%) had received two doses of the measles vaccine. Phylogenetic analysis revealed that all the sequences of the nucleoprotein gene belonged to genotype B3. CONCLUSIONS: Measles infection was more commonly confirmed among those with one recorded dose compared to suspect cases with none, unknown or two recorded doses. The molecular characterization of the strains showed the circulation of the B3 genotype which is endemic on the African continent, thirty years after the B2 genotype was described in an outbreak in Libreville, the capital of Gabon. These findings highlight that surveillance and molecular investigation of measles should be continued in Gabon.


Assuntos
Surtos de Doenças , Vírus do Sarampo/isolamento & purificação , Sarampo/virologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Gabão/epidemiologia , Variação Genética , Genótipo , Humanos , Lactente , Masculino , Sarampo/epidemiologia , Vacina contra Sarampo/administração & dosagem , Vírus do Sarampo/genética , Vírus do Sarampo/imunologia , Pessoa de Meia-Idade , Nucleoproteínas/genética , Filogenia , Reação em Cadeia da Polimerase em Tempo Real , Proteínas Virais/genética , Adulto Jovem
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