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[PMID]:28827792
[Au] Autor:Falendysz EA; Lopera JG; Doty JB; Nakazawa Y; Crill C; Lorenzsonn F; Kalemba LN; Ronderos MD; Mejia A; Malekani JM; Karem K; Carroll DS; Osorio JE; Rocke TE
[Ad] Endereço:US Geological Survey, National Wildlife Health Center, Madison, Wisconsin, United States of America.
[Ti] Título:Characterization of Monkeypox virus infection in African rope squirrels (Funisciurus sp.).
[So] Source:PLoS Negl Trop Dis;11(8):e0005809, 2017 Aug.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Monkeypox (MPX) is a zoonotic disease endemic in Central and West Africa and is caused by Monkeypox virus (MPXV), the most virulent Orthopoxvirus affecting humans since the eradication of Variola virus (VARV). Many aspects of the MPXV transmission cycle, including the natural host of the virus, remain unknown. African rope squirrels (Funisciurus spp.) are considered potential reservoirs of MPXV, as serosurveillance data in Central Africa has confirmed the circulation of the virus in these rodent species [1,2]. In order to understand the tissue tropism and clinical signs associated with infection with MPXV in these species, wild-caught rope squirrels were experimentally infected via intranasal and intradermal exposure with a recombinant MPXV strain from Central Africa engineered to express the luciferase gene. After infection, we monitored viral replication and shedding via in vivo bioluminescent imaging, viral culture and real time PCR. MPXV infection in African rope squirrels caused mortality and moderate to severe morbidity, with clinical signs including pox lesions in the skin, eyes, mouth and nose, dyspnea, and profuse nasal discharge. Both intranasal and intradermal exposures induced high levels of viremia, fast systemic spread, and long periods of viral shedding. Shedding and luminescence peaked at day 6 post infection and was still detectable after 15 days. Interestingly, one sentinel animal, housed in the same room but in a separate cage, also developed severe MPX disease and was euthanized. This study indicates that MPXV causes significant pathology in African rope squirrels and infected rope squirrels shed large quantities of virus, supporting their role as a potential source of MPXV transmission to humans and other animals in endemic MPX regions.
[Mh] Termos MeSH primário: Vírus da Varíola dos Macacos/fisiologia
Monkeypox/veterinária
Sciuridae/virologia
[Mh] Termos MeSH secundário: África Central
África Ocidental
Animais
Anticorpos Antivirais/sangue
DNA Viral/sangue
Seres Humanos
Sciuridae/imunologia
Replicação Viral
Eliminação de Partículas Virais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Viral); 0 (DNA, Viral)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170917
[Lr] Data última revisão:
170917
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170823
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005809


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[PMID]:28814515
[Au] Autor:Dyall J; Johnson RF; Chefer S; Leyson C; Thomasson D; Seidel J; Ragland DR; Byrum R; Jett C; Cann JA; St Claire M; Jagoda E; Reba RC; Hammoud D; Blaney JE; Jahrling PB
[Ad] Endereço:Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA dyallj@niaid.nih.gov.
[Ti] Título:[ F]-Fluorodeoxyglucose Uptake in Lymphoid Tissue Serves as a Predictor of Disease Outcome in the Nonhuman Primate Model of Monkeypox Virus Infection.
[So] Source:J Virol;91(21), 2017 Nov 01.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Real-time bioimaging of infectious disease processes may aid countermeasure development and lead to an improved understanding of pathogenesis. However, few studies have identified biomarkers for monitoring infections using imaging. Previously, we demonstrated that positron emission tomography/computed tomography (PET/CT) imaging with [ F]-fluorodeoxyglucose (FDG) can monitor monkeypox disease progression in nonhuman primates (NHPs). In this study, we investigated [ F]-FDG-PET/CT imaging of immune processes in lymphoid tissues to identify patterns of inflammation in the monkepox NHP model and to determine the value of [ F]-FDG-PET/CT as a biomarker for disease and treatment outcomes. Quantitative analysis of [ F]-FDG-PET/CT images revealed differences between moribund and surviving animals at two sites vital to the immune response to viral infections, bone marrow and lymph nodes (LNs). Moribund NHPs demonstrated increased [ F]-FDG uptake in bone marrow 4 days postinfection compared to surviving NHPs. In surviving, treated NHPs, increase in LN volume correlated with [ F]-FDG uptake and peaked 10 days postinfection, while minimal lymphadenopathy and higher glycolytic activity were observed in moribund NHPs early in infection. Imaging data were supported by standard virology, pathology, and immunology findings. Even with the limited number of subjects, imaging was able to differentiate the difference between disease outcomes, warranting additional studies to demonstrate whether [ F]-FDG-PET/CT can identify other, subtler effects. Visualizing altered metabolic activity at sites involved in the immune response by [ F]-FDG-PET/CT imaging is a powerful tool for identifying key disease-specific time points and locations that are most relevant for pathogenesis and treatment. Positron emission tomography and computed tomography (PET/CT) imaging is a universal tool in oncology and neuroscience. The application of this technology to infectious diseases is far less developed. We used PET/CT imaging with [ F]-labeled fluorodeoxyglucose ([ F]-FDG) in monkeys after monkeypox virus exposure to monitor the immune response in lymphoid tissues. In lymph nodes of surviving monkeys, changes in [ F]-FDG uptake positively correlated with enlargement of the lymph nodes and peaked on day 10 postinfection. In contrast, the bone marrow and lymph nodes of nonsurvivors showed increased [ F]-FDG uptake by day 4 postinfection with minimal lymph node enlargement, indicating that elevated cell metabolic activity early after infection is predictive of disease outcome. [ F]-FDG-PET/CT imaging can provide real-time snapshots of metabolic activity changes in response to viral infections and identify key time points and locations most relevant for monitoring the development of pathogenesis and for potential treatment to be effective.
[Mh] Termos MeSH primário: Citosina/análogos & derivados
Fluordesoxiglucose F18/metabolismo
Linfadenopatia/patologia
Tecido Linfoide/patologia
Vírus da Varíola dos Macacos/patogenicidade
Monkeypox/patologia
Organofosfonatos/farmacologia
Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos
[Mh] Termos MeSH secundário: Animais
Antivirais/farmacologia
Medula Óssea/diagnóstico por imagem
Medula Óssea/efeitos dos fármacos
Medula Óssea/patologia
Citosina/farmacologia
Linfadenopatia/diagnóstico por imagem
Tecido Linfoide/diagnóstico por imagem
Tecido Linfoide/efeitos dos fármacos
Macaca mulatta/virologia
Masculino
Monkeypox/diagnóstico por imagem
Monkeypox/tratamento farmacológico
Monkeypox/virologia
Prognóstico
Compostos Radiofarmacêuticos/metabolismo
Taxa de Sobrevida
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Organophosphonates); 0 (Radiopharmaceuticals); 0Z5B2CJX4D (Fluorodeoxyglucose F18); 8J337D1HZY (Cytosine); JIL713Q00N (cidofovir)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170818
[St] Status:MEDLINE


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[PMID]:28331092
[Au] Autor:Realegeno S; Puschnik AS; Kumar A; Goldsmith C; Burgado J; Sambhara S; Olson VA; Carroll D; Damon I; Hirata T; Kinoshita T; Carette JE; Satheshkumar PS
[Ad] Endereço:Poxvirus and Rabies Branch, Division of High Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
[Ti] Título:Monkeypox Virus Host Factor Screen Using Haploid Cells Identifies Essential Role of GARP Complex in Extracellular Virus Formation.
[So] Source:J Virol;91(11), 2017 Jun 01.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:(MPXV) is a human pathogen that is a member of the genus, which includes and (the causative agent of smallpox). Human monkeypox is considered an emerging zoonotic infectious disease. To identify host factors required for MPXV infection, we performed a genome-wide insertional mutagenesis screen in human haploid cells. The screen revealed several candidate genes, including those involved in Golgi trafficking, glycosaminoglycan biosynthesis, and glycosylphosphatidylinositol (GPI)-anchor biosynthesis. We validated the role of a set of vacuolar protein sorting (VPS) genes during infection, VPS51 to VPS54 (VPS51-54), which comprise the Golgi-associated retrograde protein (GARP) complex. The GARP complex is a tethering complex involved in retrograde transport of endosomes to the -Golgi apparatus. Our data demonstrate that VPS52 and VPS54 were dispensable for mature virion (MV) production but were required for extracellular virus (EV) formation. For comparison, a known antiviral compound, ST-246, was used in our experiments, demonstrating that EV titers in VPS52 and VPS54 knockout (KO) cells were comparable to levels exhibited by ST-246-treated wild-type cells. Confocal microscopy was used to examine actin tail formation, one of the viral egress mechanisms for cell-to-cell dissemination, and revealed an absence of actin tails in VPS52KO- or VPS54KO-infected cells. Further evaluation of these cells by electron microscopy demonstrated a decrease in levels of wrapped viruses (WVs) compared to those seen with the wild-type control. Collectively, our data demonstrate the role of GARP complex genes in double-membrane wrapping of MVs necessary for EV formation, implicating the host endosomal trafficking pathway in orthopoxvirus infection. Human monkeypox is an emerging zoonotic infectious disease caused by (MPXV). Of the two MPXV clades, the Congo Basin strain is associated with severe disease, increased mortality, and increased human-to-human transmission relative to the West African strain. Monkeypox is endemic in regions of western and central Africa but was introduced into the United States in 2003 from the importation of infected animals. The threat of MPXV and other orthopoxviruses is increasing due to the absence of routine smallpox vaccination leading to a higher proportion of naive populations. In this study, we have identified and validated candidate genes that are required for MPXV infection, specifically, those associated with the Golgi-associated retrograde protein (GARP) complex. Identifying host targets required for infection that prevents extracellular virus formation such as the GARP complex or the retrograde pathway can provide a potential target for antiviral therapy.
[Mh] Termos MeSH primário: Endossomos/metabolismo
Interações Hospedeiro-Patógeno
Proteínas de Membrana/genética
Vírus da Varíola dos Macacos/fisiologia
Proteínas de Transporte Vesicular/metabolismo
[Mh] Termos MeSH secundário: Actinas/efeitos dos fármacos
Actinas/metabolismo
Animais
Benzamidas/farmacologia
Transporte Biológico
Linhagem Celular
Genoma Humano
Glicosaminoglicanos/biossíntese
Glicosaminoglicanos/genética
Glicosilfosfatidilinositóis/biossíntese
Complexo de Golgi/genética
Complexo de Golgi/metabolismo
Haploidia
Seres Humanos
Isoindóis/farmacologia
Proteínas de Membrana/metabolismo
Monkeypox/virologia
Mutagênese Insercional
Proteínas de Transporte Vesicular/genética
Carga Viral
Replicação Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Actins); 0 (Benzamides); 0 (Glycosaminoglycans); 0 (Glycosylphosphatidylinositols); 0 (Isoindoles); 0 (LRRC32 protein, human); 0 (Membrane Proteins); 0 (ST-246); 0 (VPS53 protein, human); 0 (Vesicular Transport Proteins)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171112
[Lr] Data última revisão:
171112
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170324
[St] Status:MEDLINE


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[PMID]:28192435
[Au] Autor:Quiner CA; Moses C; Monroe BP; Nakazawa Y; Doty JB; Hughes CM; McCollum AM; Ibata S; Malekani J; Okitolonda E; Carroll DS; Reynolds MG
[Ad] Endereço:Division of Epidemiology and Biostatistics, School of Public Health, University of California, Berkeley, California, United States of America.
[Ti] Título:Presumptive risk factors for monkeypox in rural communities in the Democratic Republic of the Congo.
[So] Source:PLoS One;12(2):e0168664, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Monkeypox virus (MPXV), a close relative of Variola virus, is a zoonotic virus with an unknown reservoir. Interaction with infected wildlife, bites from peri-domestic animals, and bushmeat hunting are hypothesized routes of infection from wildlife to humans. Using a Risk Questionnaire, performed in monkeypox-affected areas of rural Democratic Republic of the Congo, we describe the lifestyles and demographics associated with presumptive risk factors for MPXV infection. We generated two indices to assess risk: Household Materials Index (HMI), a proxy for socioeconomic status of households and Risk Activity Index (RAI), which describes presumptive risk for animal-to-human transmission of MPXV. Based on participant self-reported activity patterns, we found that people in this population are more likely to visit the forest than a market to fulfill material needs, and that the reported occupation is limited in describing behavior of individuals may participate. Being bitten by rodents in the home was commonly reported, and this was significantly associated with a low HMI. The highest scoring RAI sub-groups were 'hunters' and males aged ≥ 18 years; however, several activities involving MPXV-implicated animals were distributed across all sub-groups. The current analysis may be useful in identifying at-risk groups and help to direct education, outreach and prevention efforts more efficiently.
[Mh] Termos MeSH primário: Monkeypox/transmissão
Saúde da População Rural/estatística & dados numéricos
População Rural/estatística & dados numéricos
[Mh] Termos MeSH secundário: Adolescente
Adulto
Animais
Animais Selvagens/virologia
República Democrática do Congo/epidemiologia
Características da Família
Feminino
Interações Hospedeiro-Patógeno
Seres Humanos
Estilo de Vida
Masculino
Monkeypox/epidemiologia
Monkeypox/virologia
Vírus da Varíola dos Macacos/fisiologia
Ocupações
Medição de Risco
Fatores de Risco
Roedores/virologia
Fatores Socioeconômicos
Inquéritos e Questionários
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170824
[Lr] Data última revisão:
170824
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170214
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0168664


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[PMID]:27994107
[Au] Autor:Li D; Wilkins K; McCollum AM; Osadebe L; Kabamba J; Nguete B; Likafi T; Balilo MP; Lushima RS; Malekani J; Damon IK; Vickery MC; Pukuta E; Nkawa F; Karhemere S; Tamfum JM; Okitolonda EW; Li Y; Reynolds MG
[Ad] Endereço:Poxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, National Center for Enteric and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia.
[Ti] Título:Evaluation of the GeneXpert for Human Monkeypox Diagnosis.
[So] Source:Am J Trop Med Hyg;96(2):405-410, 2017 Feb 08.
[Is] ISSN:1476-1645
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Monkeypox virus (MPXV), a zoonotic orthopoxvirus (OPX), is endemic in the Democratic Republic of Congo (DRC). Currently, diagnostic assays for human monkeypox (MPX) focus on real-time quantitative polymerase chain reaction (PCR) assays, which are typically performed in sophisticated laboratory settings. Herein, we evaluated the accuracy and utility of a multiplex MPX assay using the GeneXpert platform, a portable rapid diagnostic device that may serve as a point-of-care test to diagnose infections in endemic areas. The multiplex MPX/OPX assay includes a MPX-specific PCR test, OPX-generic PCR test, and an internal control PCR test. In total, 164 diagnostic specimens (50 crusts and 114 vesicular swabs) were collected from suspected MPX cases in Tshuapa Province, DRC, under national surveillance guidelines. The specimens were tested with the GeneXpert MPX/OPX assay and an OPX PCR assay at the Institut National de Recherche Biomedicale (INRB) in Kinshasa. Aliquots of each specimen were tested in parallel with a MPX-specific PCR assay at the Centers for Disease Control and Prevention. The results of the MPX PCR were used as the gold standard for all analyses. The GeneXpert MPX/OPX assay performed at INRB had a sensitivity of 98.8% and specificity of 100%. The GeneXpert assay performed well with both crust and vesicle samples. The GeneXpert MPX/OPX test incorporates a simple methodology that performs well in both laboratory and field conditions, suggesting its viability as a diagnostic platform that may expand and expedite current MPX detection capabilities.
[Mh] Termos MeSH primário: Vírus da Varíola dos Macacos/genética
Monkeypox/diagnóstico
Monkeypox/genética
Reação em Cadeia da Polimerase/métodos
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Idoso de 80 Anos ou mais
Criança
Pré-Escolar
República Democrática do Congo/epidemiologia
Feminino
Seres Humanos
Lactente
Recém-Nascido
Masculino
Meia-Idade
Monkeypox/epidemiologia
Sistemas Automatizados de Assistência Junto ao Leito
Sensibilidade e Especificidade
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170531
[Lr] Data última revisão:
170531
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:161221
[St] Status:MEDLINE
[do] DOI:10.4269/ajtmh.16-0567


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[PMID]:25944444
[Au] Autor:Sergeev AA; Kabanov AS; Bulychev LE; Sergeev AA; Pyankov OV; Bodnev SA; Galahova DO; Zamedyanskaya AS; Titova KA; Glotova TI; Taranov OS; Omigov VV; Shishkina LN; Agafonov AP; Sergeev AN
[Ad] Endereço:Federal Budgetary Research Institution - State Research Center of Virology and Biotechnology VECTOR, Federal Service for Surveillance on Consumer Rights Protection and Human Well-being, Koltsovo, Russia.
[Ti] Título:Using the Ground Squirrel (Marmota bobak) as an Animal Model to Assess Monkeypox Drug Efficacy.
[So] Source:Transbound Emerg Dis;64(1):226-236, 2017 Feb.
[Is] ISSN:1865-1682
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:In experiments to study the sensitivity of ground squirrels (Marmota bobak) to monkeypox virus (MPXV) at intranasal challenge, expressed pox-like clinical symptoms (hyperthermia, lymphadenitis, skin rash all over the body and mucous membranes and others) were observed 7-9 days post-infection. The 50% infective dose (ID ) of MPXV for these marmots determined by the presence of clinical signs of the disease was 2.2 log PFU. Some diseased marmots (about 40%) died 13-22 days post-infection, and the mortality rate was weakly dependent on MPXV infective dose. Lungs with trachea were primary target organs of marmots challenged intranasally (with ~30 ID ). The pathogen got to secondary target organs of the animals mainly via the lymphatic way (with replication in bifurcation lymph nodes). Lungs with trachea, nasal mucosa and skin were the organs where the maximum MPXV amounts accumulated in these animals. Evidences of the pathogen presence and replication were revealed in these and subcutaneously infected marmots in the traditional primary target cells for MPXV (macrophages and respiratory tract epitheliocytes), as well as in some other cells (endotheliocytes, plasmocytes, fibroblasts, reticular and smooth muscle cells). Our use of this animal species to assess the antiviral efficacy of some drugs demonstrated the agreement of the obtained results with those described in scientific literature, which opens up the prospects of using marmots as animal models for monkeypox to develop therapeutic and preventive anti-smallpox drugs.
[Mh] Termos MeSH primário: Antivirais/efeitos adversos
Marmota
Vírus da Varíola dos Macacos/efeitos dos fármacos
Monkeypox/veterinária
[Mh] Termos MeSH secundário: Administração Intranasal/veterinária
Animais
Modelos Animais de Doenças
Feminino
Masculino
Monkeypox/tratamento farmacológico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170215
[Lr] Data última revisão:
170215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150507
[St] Status:MEDLINE
[do] DOI:10.1111/tbed.12364


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[PMID]:27783372
[Au] Autor:Kalthan E; Dondo-Fongbia JP; Yambele S; Dieu-Creer LR; Zepio R; Pamatika CM
[Ad] Endereço:Direction de la région sanitaire No6, Bangui, République centrafricaine. kalthanernest@yahoo.fr.
[Ti] Título:[Twelve cases of monkeypox virus outbreak in Bangassou District (Central African Republic) in December 2015].
[Ti] Título:Epidémie de 12 cas de maladie à virus monkeypox dans le district de Bangassou en République Centrafricaine en décembre 2015..
[So] Source:Bull Soc Pathol Exot;109(5):358-363, 2016 Dec.
[Is] ISSN:0037-9085
[Cp] País de publicação:France
[La] Idioma:fre
[Ab] Resumo:An outbreak of monkeypox occurred in the district of Bangassou in 2015. The monkeypox is a re-emerging zoonosis of viral origin highly contagious. It is an eruptive fever which evolves in an epidemic manner. An investigation was held December 10, 2015, to February 10, 2016 in the focus of the epidemic. Its objective was to describe the epidemic according to the time, places and people and to determine the incidence and lethality of the disease. This was a descriptive study. The data collection was made by interview and using a linear plug composed of several sections. All suspected cases were taken into account. The interview was done with patients or the parents of sick children. The blood and the contents of the lesions were collected and sent to the laboratory of the Institut Pasteur in Bangui for confirmation. Our data were analyzed with Epi info7. In total 12 patients had been registered including 9 secondary cases. Patients aged 31 to 40 years and less than 10 years were most affected. In addition, adults were most affected by the disease (8/12). The average age was 25 years with extremes at 15 months and 41 years. The sex male/female ratio was 1. The overall attack rate of disease and lethality were 0.2 per 1000 inhabitants and 25% respectively. The fatality was 67% among children less than 10 years. Fever and rash were the main symptoms of the disease. Lymphadenopathy was present in 54.5%. Ten of the 12 patients were hospitalized (83%). The average duration of hospitalization was 13 days with the extremes 6 and 28 days. The monkeypox like smallpox remains a serious and fatal disease in children. A survey of animal reservoirs complained to identify strains of the virus is essential. During an outbreak, good communication and isolation of patients may break the chain of transmission. Other measures to limit their contact with the forest or virus reservoirs are to be encouraged.
[Mh] Termos MeSH primário: Surtos de Doenças
Monkeypox/epidemiologia
Zoonoses/epidemiologia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Animais
República Centro-Africana
Criança
Pré-Escolar
Epidemias
Feminino
Seres Humanos
Lactente
Masculino
Monkeypox/diagnóstico
Vírus da Varíola dos Macacos/isolamento & purificação
Adulto Jovem
Zoonoses/virologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170303
[Lr] Data última revisão:
170303
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161027
[St] Status:MEDLINE
[do] DOI:10.1007/s13149-016-0516-z


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[PMID]:27768891
[Au] Autor:Gilchuk I; Gilchuk P; Sapparapu G; Lampley R; Singh V; Kose N; Blum DL; Hughes LJ; Satheshkumar PS; Townsend MB; Kondas AV; Reed Z; Weiner Z; Olson VA; Hammarlund E; Raue HP; Slifka MK; Slaughter JC; Graham BS; Edwards KM; Eisenberg RJ; Cohen GH; Joyce S; Crowe JE
[Ad] Endereço:The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
[Ti] Título:Cross-Neutralizing and Protective Human Antibody Specificities to Poxvirus Infections.
[So] Source:Cell;167(3):684-694.e9, 2016 Oct 20.
[Is] ISSN:1097-4172
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Monkeypox (MPXV) and cowpox (CPXV) are emerging agents that cause severe human infections on an intermittent basis, and variola virus (VARV) has potential for use as an agent of bioterror. Vaccinia immune globulin (VIG) has been used therapeutically to treat severe orthopoxvirus infections but is in short supply. We generated a large panel of orthopoxvirus-specific human monoclonal antibodies (Abs) from immune subjects to investigate the molecular basis of broadly neutralizing antibody responses for diverse orthopoxviruses. Detailed analysis revealed the principal neutralizing antibody specificities that are cross-reactive for VACV, CPXV, MPXV, and VARV and that are determinants of protection in murine challenge models. Optimal protection following respiratory or systemic infection required a mixture of Abs that targeted several membrane proteins, including proteins on enveloped and mature virion forms of virus. This work reveals orthopoxvirus targets for human Abs that mediate cross-protective immunity and identifies new candidate Ab therapeutic mixtures to replace VIG.
[Mh] Termos MeSH primário: Anticorpos Monoclonais/imunologia
Anticorpos Neutralizantes/imunologia
Anticorpos Antivirais/imunologia
Especificidade de Anticorpos
Infecções por Poxviridae/imunologia
[Mh] Termos MeSH secundário: Varíola Bovina/imunologia
Vírus da Varíola Bovina/imunologia
Reações Cruzadas
Seres Humanos
Leucócitos Mononucleares/imunologia
Monkeypox/imunologia
Vírus da Varíola dos Macacos/imunologia
Varíola/imunologia
Vaccinia/imunologia
Vírus Vaccinia/imunologia
Vírus da Varíola/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, N.I.H., INTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Antibodies, Neutralizing); 0 (Antibodies, Viral)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:171020
[Lr] Data última revisão:
171020
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161022
[St] Status:MEDLINE


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[PMID]:27585810
[Au] Autor:Zhao K; Wohlhueter RM; Li Y
[Ad] Endereço:Office of Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, 30333, USA. vzt5@cdc.gov.
[Ti] Título:Finishing monkeypox genomes from short reads: assembly analysis and a neural network method.
[So] Source:BMC Genomics;17 Suppl 5:497, 2016 08 31.
[Is] ISSN:1471-2164
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Poxviruses constitute one of the largest and most complex animal virus families known. The notorious smallpox disease has been eradicated and the virus contained, but its simian sister, monkeypox is an emerging, untreatable infectious disease, killing 1 to 10 % of its human victims. In the case of poxviruses, the emergence of monkeypox outbreaks in humans and the need to monitor potential malicious release of smallpox virus requires development of methods for rapid virus identification. Whole-genome sequencing (WGS) is an emergent technology with increasing application to the diagnosis of diseases and the identification of outbreak pathogens. But "finishing" such a genome is a laborious and time-consuming process, not easily automated. To date the large, complete poxvirus genomes have not been studied comprehensively in terms of applying WGS techniques and evaluating genome assembly algorithms. RESULTS: To explore the limitations to finishing a poxvirus genome from short reads, we first analyze the repetitive regions in a monkeypox genome and evaluate genome assembly on the simulated reads. We also report on procedures and insights relevant to the assembly (from realistically short reads) of genomes. Finally, we propose a neural network method (namely Neural-KSP) to "finish" the process by closing gaps remaining after conventional assembly, as the final stage in a protocol to elucidate clinical poxvirus genomic sequences. CONCLUSIONS: The protocol may prove useful in any clinical viral isolate (regardless if a reference-strain sequence is available) and especially useful in genomes confounded by many global and local repetitive sequences embedded in them. This work highlights the feasibility of finishing real, complex genomes by systematically analyzing genetic characteristics, thus remedying existing assembly shortcomings with a neural network method. Such finished sequences may enable clinicians to track genetic distance between viral isolates that provides a powerful epidemiological tool.
[Mh] Termos MeSH primário: Genoma Viral
Vírus da Varíola dos Macacos/genética
[Mh] Termos MeSH secundário: Sequenciamento de Nucleotídeos em Larga Escala
Seres Humanos
Monkeypox/virologia
Redes Neurais (Computação)
Análise de Sequência de DNA
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, U.S. GOV'T, P.H.S.
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171119
[Lr] Data última revisão:
171119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160903
[St] Status:MEDLINE
[do] DOI:10.1186/s12864-016-2826-8


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[PMID]:27477914
[Au] Autor:Maksyutov RA; Gavrilova EV; Shchelkunov SN
[Ad] Endereço:State Research Center of Virology and Biotechnology "VECTOR", Koltsovo, Novosibirsk Region, 630559, Russia. Electronic address: maksrinat@yandex.ru.
[Ti] Título:Species-specific differentiation of variola, monkeypox, and varicella-zoster viruses by multiplex real-time PCR assay.
[So] Source:J Virol Methods;236:215-220, 2016 Oct.
[Is] ISSN:1879-0984
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:A method of one-stage rapid detection and differentiation of epidemiologically important variola virus (VARV), monkeypox virus (MPXV), and varicella-zoster virus (VZV) utilizing multiplex real-time TaqMan PCR assay was developed. Four hybridization probes with various fluorescent dyes and the corresponding fluorescence quenchers were simultaneously used for the assay. The hybridization probes specific for the VARV sequence contained FAM/BHQ1 as a dye/quencher pair; MPXV-specific, JOE/BHQ1; VZV-specific, TAMRA/BHQ2; and internal control-specific, Cy5/BHQ3. The specificity and sensitivity of the developed method were assessed by analyzing DNA of 32 strains belonging to orthopoxvirus and herpesvirus species.
[Mh] Termos MeSH primário: Herpesvirus Humano 3/isolamento & purificação
Vírus da Varíola dos Macacos/isolamento & purificação
Reação em Cadeia da Polimerase Multiplex/métodos
Reação em Cadeia da Polimerase em Tempo Real/métodos
Vírus da Varíola/isolamento & purificação
Virologia/métodos
[Mh] Termos MeSH secundário: Herpesvirus Humano 3/classificação
Herpesvirus Humano 3/genética
Vírus da Varíola dos Macacos/classificação
Vírus da Varíola dos Macacos/genética
Sensibilidade e Especificidade
Vírus da Varíola/classificação
Vírus da Varíola/genética
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171004
[Lr] Data última revisão:
171004
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160802
[St] Status:MEDLINE



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