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[PMID]:28555548
[Au] Autor:López-Bueno A; Parras-Moltó M; López-Barrantes O; Belda S; Alejo A
[Ad] Endereço:1​Centro de Biología Molecular 'Severo Ochoa' (Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid), Cantoblanco, Madrid 28049, Spain.
[Ti] Título:Recombination events and variability among full-length genomes of co-circulating molluscum contagiosum virus subtypes 1 and 2.
[So] Source:J Gen Virol;98(5):1073-1079, 2017 May.
[Is] ISSN:1465-2099
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Molluscum contagiosum virus (MCV) is the sole member of the Molluscipoxvirus genus and causes a highly prevalent human disease of the skin characterized by the formation of a variable number of lesions that can persist for prolonged periods of time. Two major genotypes, subtype 1 and subtype 2, are recognized, although currently only a single complete genomic sequence corresponding to MCV subtype 1 is available. Using next-generation sequencing techniques, we report the complete genomic sequence of four new MCV isolates, including the first one derived from a subtype 2. Comparisons suggest a relatively distant evolutionary split between both MCV subtypes. Further, our data illustrate concurrent circulation of distinct viruses within a population and reveal the existence of recombination events among them. These results help identify a set of MCV genes with potentially relevant roles in molluscum contagiosum epidemiology and pathogenesis.
[Mh] Termos MeSH primário: Genoma Viral
Vírus do Molusco Contagioso/classificação
Vírus do Molusco Contagioso/genética
Recombinação Genética
[Mh] Termos MeSH secundário: Criança
Análise por Conglomerados
Voluntários Saudáveis
Sequenciamento de Nucleotídeos em Larga Escala
Seres Humanos
Vírus do Molusco Contagioso/crescimento & desenvolvimento
Vírus do Molusco Contagioso/isolamento & purificação
Filogenia
Análise de Sequência de DNA
Homologia de Sequência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170713
[Lr] Data última revisão:
170713
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170531
[St] Status:MEDLINE
[do] DOI:10.1099/jgv.0.000759


  2 / 253 MEDLINE  
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[PMID]:28515292
[Au] Autor:Biswas S; Shisler JL
[Ad] Endereço:Department of Microbiology, University of Illinois, Urbana-Champaign, Urbana, Illinois, USA.
[Ti] Título:Molluscum Contagiosum Virus MC159 Abrogates cIAP1-NEMO Interactions and Inhibits NEMO Polyubiquitination.
[So] Source:J Virol;91(15), 2017 Aug 01.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Molluscum contagiosum virus (MCV) is a dermatotropic poxvirus that causes benign skin lesions. MCV lesions persist because of virally encoded immune evasion molecules that inhibit antiviral responses. The MCV MC159 protein suppresses NF-κB activation, a powerful antiviral response, via interactions with the NF-κB essential modulator (NEMO) subunit of the IκB kinase (IKK) complex. Binding of MC159 to NEMO does not disrupt the IKK complex, implying that MC159 prevents IKK activation via an as-yet-unidentified strategy. Here, we demonstrated that MC159 inhibited NEMO polyubiquitination, a posttranslational modification required for IKK and downstream NF-κB activation. Because MCV cannot be propagated in cell culture, MC159 was expressed independent of infection or during a surrogate vaccinia virus infection to identify how MC159 prevented polyubiquitination. Cellular inhibitor of apoptosis protein 1 (cIAP1) is a cellular E3 ligase that ubiquitinates NEMO. Mutational analyses revealed that MC159 and cIAP1 each bind to the same NEMO region, suggesting that MC159 may competitively inhibit cIAP1-NEMO interactions. Indeed, MC159 prevented cIAP1-NEMO interactions. MC159 also diminished cIAP1-mediated NEMO polyubiquitination and cIAP1-induced NF-κB activation. These data suggest that MC159 competitively binds to NEMO to prevent cIAP1-induced NEMO polyubiquitination. To our knowledge, this is the first report of a viral protein disrupting NEMO-cIAP1 interactions to strategically suppress IKK activation. All viruses must antagonize antiviral signaling events for survival. We hypothesize that MC159 inhibits NEMO polyubiquitination as a clever strategy to manipulate the host cell environment to the benefit of the virus. Molluscum contagiosum virus (MCV) is a human-specific poxvirus that causes persistent skin neoplasms. The persistence of MCV has been attributed to viral downregulation of host cell immune responses such as NF-κB activation. We show here that the MCV MC159 protein interacts with the NEMO subunit of the IKK complex to prevent NEMO interactions with the cIAP1 E3 ubiquitin ligase. This interaction correlates with a dampening of cIAP1 to polyubiquitinate NEMO and to activate NF-κB. This inhibition of cIAP1-NEMO interactions is a new viral strategy to minimize IKK activation and to control NEMO polyubiquitination. This research provides new insights into mechanisms that persistent viruses may use to cause long-term infection of host cells.
[Mh] Termos MeSH primário: Interações Hospedeiro-Patógeno
Quinase I-kappa B/antagonistas & inibidores
Proteínas Inibidoras de Apoptose/antagonistas & inibidores
Vírus do Molusco Contagioso/patogenicidade
Processamento de Proteína Pós-Traducional
Ubiquitinação
Proteínas Virais/metabolismo
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Seres Humanos
Camundongos
Ligação Proteica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (IKBKG protein, human); 0 (Inhibitor of Apoptosis Proteins); 0 (Viral Proteins); 0 (viral FLIP protein, Molluscum contagiosum virus); EC 2.7.11.10 (I-kappa B Kinase)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171025
[Lr] Data última revisão:
171025
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170519
[St] Status:MEDLINE


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[PMID]:28490597
[Au] Autor:Brady G; Haas DA; Farrell PJ; Pichlmair A; Bowie AG
[Ad] Endereço:School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland bradyg1@tcd.ie agbowie@tcd.ie.
[Ti] Título:Molluscum Contagiosum Virus Protein MC005 Inhibits NF-κB Activation by Targeting NEMO-Regulated IκB Kinase Activation.
[So] Source:J Virol;91(15), 2017 Aug 01.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Molluscum contagiosum virus (MCV), the only known extant human-adapted poxvirus, causes a long-duration infection characterized by skin lesions that typically display an absence of inflammation despite containing high titers of live virus. Despite this curious presentation, MCV is very poorly characterized in terms of host-pathogen interactions. The absence of inflammation around MCV lesions suggests the presence of potent inhibitors of human antiviral immunity and inflammation. However, only a small number of MCV immunomodulatory genes have been characterized in detail. It is likely that many more remain to be discovered, given the density of such sequences in other poxvirus genomes. NF-κB activation occurs in response to both virus-induced pattern recognition receptor (PRR) signaling and cellular activation by virus-induced proinflammatory cytokines like tumor necrosis factor and interleukin-1. Activated NF-κB drives cytokine and interferon gene expression, leading to inflammation and virus clearance. We report that MC005, which has no orthologs in other poxvirus genomes, is a novel inhibitor of PRR- and cytokine-stimulated NF-κB activation. MC005 inhibited NF-κB proximal to the IκB kinase (IKK) complex, and unbiased affinity purification revealed that MC005 interacts with the IKK subunit NEMO (NF-κB essential modulator). MC005 binding to NEMO prevents the conformational priming of the IKK complex that occurs when NEMO binds to ubiquitin chains during pathway activation. These data reveal a novel mechanism of poxvirus inhibition of human innate immunity, validate current dynamic models of NEMO-dependent IKK complex activation, and further clarify how the human-adapted poxvirus MCV can so effectively evade antiviral immunity and suppress inflammation to persist in human skin lesions. Poxviruses adapt to specific hosts over time, evolving and tailoring elegantly precise inhibitors of the rate-limiting steps within the signaling pathways that control innate immunity and inflammation. These inhibitors reveal new features of the antiviral response, clarify existing models of signaling regulation while offering potent new tools for approaching therapeutic intervention in autoimmunity and inflammatory disease. Molluscum contagiosum virus (MCV) is the only known extant poxvirus specifically adapted to human infection and appears adept at evading normal human antiviral responses, yet it remains poorly characterized. We report the identification of MCV protein MC005 as an inhibitor of the pathways leading to the activation of NF-κB, an essential regulator of innate immunity. Further, identification of the mechanism of inhibition of NF-κB by MC005 confirms current models of the complex way in which NF-κB is regulated and greatly expands our understanding of how MCV so effectively evades human immunity.
[Mh] Termos MeSH primário: Interações Hospedeiro-Patógeno
Quinase I-kappa B/antagonistas & inibidores
Evasão da Resposta Imune
Vírus do Molusco Contagioso/patogenicidade
NF-kappa B/antagonistas & inibidores
Proteínas Virais/metabolismo
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (IKBKG protein, human); 0 (NF-kappa B); 0 (Viral Proteins); EC 2.7.11.10 (I-kappa B Kinase)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170726
[Lr] Data última revisão:
170726
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170512
[St] Status:MEDLINE


  4 / 253 MEDLINE  
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[PMID]:28235685
[Au] Autor:Coutu J; Ryerson MR; Bugert J; Brian Nichols D
[Ad] Endereço:Department of Biological Sciences, Seton Hall University, 400 S. Orange Ave, South Orange, NJ 07079, United States.
[Ti] Título:The Molluscum Contagiosum Virus protein MC163 localizes to the mitochondria and dampens mitochondrial mediated apoptotic responses.
[So] Source:Virology;505:91-101, 2017 May.
[Is] ISSN:1096-0341
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Apoptosis is a powerful host cell defense to prevent viruses from completing replication. Poxviruses have evolved complex means to dampen cellular apoptotic responses. The poxvirus, Molluscum Contagiosum Virus (MCV), encodes numerous host interacting molecules predicted to antagonize immune responses. However, the function of the majority of these MCV products has not been characterized. Here, we show that the MCV MC163 protein localized to the mitochondria via an N-terminal mitochondrial localization sequence and transmembrane domain. Transient expression of the MC163 protein prevented mitochondrial membrane permeabilization (MMP), an event central to cellular apoptotic responses, induced by either Tumor Necrosis Factor alpha (TNF-α) or carbonyl cyanide 3-chlorophenylhydrazone (CCCP). MC163 expression prevented the release of a mitochondrial intermembrane space reporter protein when cells were challenged with TNF-α. Inhibition of MMP was also observed in cell lines stably expressing MC163. MC163 expression may contribute to the persistence of MCV lesions by dampening cellular apoptotic responses.
[Mh] Termos MeSH primário: Permeabilidade da Membrana Celular/fisiologia
Mitocôndrias/metabolismo
Membranas Mitocondriais/metabolismo
Vírus do Molusco Contagioso/metabolismo
Proteínas Virais/metabolismo
[Mh] Termos MeSH secundário: Apoptose
Caspase 3/metabolismo
Linhagem Celular Tumoral
Células HeLa
Seres Humanos
Hidrazonas/farmacologia
Molusco Contagioso/virologia
Poli(ADP-Ribose) Polimerase-1/metabolismo
Estaurosporina/farmacologia
Fator de Necrose Tumoral alfa/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hydrazones); 0 (MC163 protein, Molluscum Contagiosum virus); 0 (Tumor Necrosis Factor-alpha); 0 (Viral Proteins); 14046-96-9 (carbonyl 3-chlorophenylhydrazone); EC 2.4.2.30 (PARP1 protein, human); EC 2.4.2.30 (Poly (ADP-Ribose) Polymerase-1); EC 3.4.22.- (Caspase 3); H88EPA0A3N (Staurosporine)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170526
[Lr] Data última revisão:
170526
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170226
[St] Status:MEDLINE


  5 / 253 MEDLINE  
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[PMID]:27607603
[Au] Autor:Horiguchi Y; Horiguchi J; Maeno KI
[Ad] Endereço:Horiguchi Clinic of Dermatology, Hirakata, Japan.
[Ti] Título:Vascular network tightly enclosing lesions of molluscum contagiosum: Basket-like capillaries of molluscum.
[So] Source:J Dermatol;44(1):52-58, 2017 Jan.
[Is] ISSN:1346-8138
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Immunohistochemical studies of one typical and two atypical cases of molluscum contagiosum with anti-CD34 monoclonal antibodies showed a tightly enclosing fine vasculature around the lesional masses of the disease. The thin interstitial septa between the lobules of the molluscum lesions also contained abundant endothelium. An electron microscopic study of a pinched-off lesion of common molluscum contagiosum demonstrated that the tightly enclosing blood vessels lacked muscle layers, suggesting that they were capillaries, being a distance of several hundred nanometers from the basal cells of the molluscum mass. A 3D constructed image of the vasculature confirmed a network of the vessels. These tightly enclosing vascular networks around the lesions of molluscum contagiosum support the rapid growth of this disease.
[Mh] Termos MeSH primário: Capilares/ultraestrutura
Molusco Contagioso/patologia
Vírus do Molusco Contagioso/isolamento & purificação
[Mh] Termos MeSH secundário: Adolescente
Antígenos CD34/metabolismo
Pré-Escolar
Dermoscopia
Feminino
Seres Humanos
Processamento de Imagem Assistida por Computador
Imagem Tridimensional
Imuno-Histoquímica
Microscopia Eletrônica
Molusco Contagioso/diagnóstico por imagem
Molusco Contagioso/virologia
Pele/irrigação sanguínea
Pele/patologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD34)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170717
[Lr] Data última revisão:
170717
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160909
[St] Status:MEDLINE
[do] DOI:10.1111/1346-8138.13519


  6 / 253 MEDLINE  
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[PMID]:27898140
[Au] Autor:Hammarin AL; Eklund Y; Karlberg M; Bogh M; Sikora P
[Ad] Endereço:Folkhalsomyndigheten - Department of Microbiology Solna, Sweden Folkhalsomyndigheten - Department of Microbiology Solna, Sweden.
[Ti] Título:[New subtype of molluscipoxvirus detected].
[Ti] Título:Ny subtyp av molluscipoxvirus påvisad - Modern teknik identifierar nya och ovanliga patogener snabbare..
[So] Source:Lakartidningen;113, 2016 11 28.
[Is] ISSN:1652-7518
[Cp] País de publicação:Sweden
[La] Idioma:swe
[Ab] Resumo:Molluscum contagiosum is a viral infection of the epidermis characterized by skin-colored papules or nodules frequently with a central depression. Atypical variants may occur, primarily in immunosuppressed individuals. We here report a case of ¼giant Molluscum contagiosum« in an immunocompetent child. The patient was presented with a fairly smooth nodule of 2 cm in diameter on the ring finger. Molluscipoxvirus-like virus particles were detected by electron microscopy from the nodule, but since the clinical picture was not compatible with MC, next generation sequencing was performed in order to verify the diagnosis.  Of the total number of obtained sequences, 25% belonged to molluscipoxvirus (MCV) and de novo assembly revealed three contigs corresponding to 95% of the MCV genome. The assembled genome was compared to previously published sequences of the ¼major envelope protein« used for genotyping of MCV genus. Several unique single nucleotide polymorphisms were identified, which led us to classify this virus as a new subtype of MCV.
[Mh] Termos MeSH primário: Molusco Contagioso/diagnóstico
Vírus do Molusco Contagioso/isolamento & purificação
[Mh] Termos MeSH secundário: Pré-Escolar
Feminino
Dedos/virologia
Sequenciamento de Nucleotídeos em Larga Escala
Seres Humanos
Microscopia Eletrônica
Vírus do Molusco Contagioso/genética
Análise de Sequência de DNA
[Pt] Tipo de publicação:CASE REPORTS
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161130
[St] Status:MEDLINE


  7 / 253 MEDLINE  
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[PMID]:26990479
[Au] Autor:Alam MS; Shrirao N
[Ad] Endereço:Medical Research Foundation, Sankara Nethralaya, Chennai.
[Ti] Título:Giant molluscum contagiosum presenting as lid neoplasm in an immunocompetent child.
[So] Source:Dermatol Online J;22(1), 2016 Jan 15.
[Is] ISSN:1087-2108
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A three-year-old boy presented to our oculoplastic clinic with complaints of painless gradually increasing right upper lid mass for the last 6 months. On examination a firm mass measuring roughly 1x1 cm was present on the upper lid. The mass was non tender with fine superficial vessels running over it. A differential diagnosis of epidermoid cyst, vascular malformation, pilomatrixoma, and juvenile xanthogranuloma was considered. The patient underwent excisional biopsy of the mass. On gross examination the mass had a brain like appearance. Histopathological examination confirmed the diagnosis of molluscum contagiosum. It is rare for molluscum contagiosum to present as a solitary lid tumor. A brain like appearance of the excised mass can provide a clue towards the diagnosis.
[Mh] Termos MeSH primário: Neoplasias Palpebrais/diagnóstico
Pálpebras/patologia
Hospedeiro Imunocomprometido
Molusco Contagioso/diagnóstico
Dermatopatias Virais/diagnóstico
[Mh] Termos MeSH secundário: Anticorpos Antivirais/análise
Pré-Escolar
Procedimentos Cirúrgicos Dermatológicos/métodos
Diagnóstico Diferencial
Pálpebras/cirurgia
Pálpebras/virologia
Seres Humanos
Masculino
Molusco Contagioso/cirurgia
Vírus do Molusco Contagioso/imunologia
Dermatopatias Virais/cirurgia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Viral)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170110
[Lr] Data última revisão:
170110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160319
[St] Status:MEDLINE


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[PMID]:26889040
[Au] Autor:Mendez-Rios JD; Yang Z; Erlandson KJ; Cohen JI; Martens CA; Bruno DP; Porcella SF; Moss B
[Ad] Endereço:Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
[Ti] Título:Molluscum Contagiosum Virus Transcriptome in Abortively Infected Cultured Cells and a Human Skin Lesion.
[So] Source:J Virol;90(9):4469-80, 2016 May.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:UNLABELLED: Molluscum contagiosum virus (MOCV), the only circulating human-specific poxvirus, has a worldwide distribution and causes benign skin lesions that may persist for months in young children and severe infections in immunosuppressed adults. Studies of MOCV are restricted by the lack of an efficient animal model or a cell culture replication system. We used next-generation sequencing to analyze and compare polyadenylated RNAs from abortive MOCV infections of several cell lines and a human skin lesion. Viral RNAs were detected for 14 days after MOCV infection of cultured cells; however, there was little change in the RNA species during this time and a similar pattern occurred in the presence of an inhibitor of protein synthesis, indicating a block preventing postreplicative gene expression. Moreover, a considerable number of MOCV RNAs mapped to homologs of orthopoxvirus early genes, but few did so to homologs of intermediate or late genes. The RNAs made during in vitro infections represent a subset of RNAs detected in human skin lesions which mapped to homologs of numerous postreplicative as well as early orthopoxvirus genes. Transfection experiments using fluorescent protein and luciferase reporters demonstrated that vaccinia virus recognized MOCV intermediate and late promoters, indicating similar gene regulation. The specific recognition of the intermediate promoter in MOCV-infected cells provided evidence for the synthesis of intermediate transcription factors, which are products of early genes, but not for late transcription factors. Transcriptome sequencing (RNA-seq) and reporter gene assays may be useful for testing engineered cell lines and conditions that ultimately could provide an in vitro replication system. IMPORTANCE: The inability to propagate molluscum contagiosum virus, which causes benign skin lesions in young children and more extensive infections in immunosuppressed adults, has constrained our understanding of the biology of this human-specific virus. In the present study, we characterized the RNAs synthesized in abortively infected cultured cells and a human skin lesion by next-generation sequencing. These studies provided an initial transcription map of the MOCV genome, suggested temporal regulation of gene expression, and indicated that the in vitro replication block occurs prior to intermediate and late gene expression. RNA-seq and reporter assays, as described here, may help to further evaluate MOCV gene expression and define conditions that could enable MOCV replication in vitro.
[Mh] Termos MeSH primário: Regulação Viral da Expressão Gênica
Molusco Contagioso/patologia
Molusco Contagioso/virologia
Vírus do Molusco Contagioso/genética
Transcriptoma
[Mh] Termos MeSH secundário: Linhagem Celular
Células Cultivadas
Biologia Computacional/métodos
Sequência Consenso
Perfilação da Expressão Gênica
Ordem dos Genes
Genes Virais
Genoma Viral
Seres Humanos
Anotação de Sequência Molecular
Vírus do Molusco Contagioso/ultraestrutura
Regiões Promotoras Genéticas
RNA Viral
Análise de Sequência de DNA
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., INTRAMURAL
[Nm] Nome de substância:
0 (RNA, Viral)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:161019
[Lr] Data última revisão:
161019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160219
[St] Status:MEDLINE
[do] DOI:10.1128/JVI.02911-15


  9 / 253 MEDLINE  
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[PMID]:26719271
[Au] Autor:Hüttmann J; Krause E; Schommartz T; Brune W
[Ad] Endereço:Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
[Ti] Título:Functional Comparison of Molluscum Contagiosum Virus vFLIP MC159 with Murine Cytomegalovirus M36/vICA and M45/vIRA Proteins.
[So] Source:J Virol;90(6):2895-905, 2015 Dec 30.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:UNLABELLED: Molluscum contagiosum virus (MCV) gene MC159 encodes a viral FLICE inhibitory protein (vFLIP) that inhibits caspase-8-mediated apoptosis. The MC159 protein was also reported to inhibit programmed necrosis (necroptosis) and modulate NF-κB activation by interacting with RIP1 and NEMO. The importance of MC159 during MCV infection has remained unknown, as there is no system for propagation and genetic manipulation of this virus. Here we investigated the functions of MC159 during viral infection using murine cytomegalovirus (MCMV) as a surrogate virus. MC159 was inserted into the MCMV genome, replacing M36 or M45, two MCMV genes with functions similar to those reported for MC159. M36 encodes a viral inhibitor of caspase-8-induced apoptosis (vICA) and M45 a viral inhibitor of RIP activation (vIRA), which inhibits RIP1/RIP3-mediated necroptosis. The M45 protein also blocks NF-κB activation by interacting with NEMO. When expressed by MCMV, MC159 blocked tumor necrosis factor alpha (TNF-α)-induced apoptosis of infected cells and partially restored MCMV replication in macrophages. However, MC159 did not fully replace M45, as it did not inhibit necroptosis in murine cells, but it reduced TNF-α-induced necroptosis in MCMV-infected human HT-29 cells. MC159 also differed from M45 in its effect on NF-κB. While MCMV-encoded M45 blocked NF-κB activation by TNF-α and interleukin-1ß (IL-1ß), MC159 inhibited TNF-α- but not IL-1ß-induced NF-κB activation in infected mouse fibroblasts. These results indicate that the spectrum of MC159's functions differs depending on cell type and expression system and that a cell culture system for the propagation of MCV is needed to determine the biological relevance of presumed viral gene functions. IMPORTANCE: MCV is a human-pathogenic poxvirus that cannot be propagated in cell culture or laboratory animals. Therefore, MCV gene products have been studied predominantly in cells expressing individual viral genes. In this study, we analyzed the function of the MCV gene MC159 by expressing it from a different virus and comparing its functions to those of two well-characterized MCMV genes. In this system, MC159 displayed some but not all of the previously described functions, suggesting that the functions of a viral gene depend on the conditions under which it is expressed. Until a cell culture system for the analysis of MCV becomes available, it might be necessary to analyze MCV genes in several different systems to extrapolate their biological importance.
[Mh] Termos MeSH primário: Proteínas Reguladoras de Apoptose/metabolismo
Fatores Imunológicos/metabolismo
Vírus do Molusco Contagioso/fisiologia
Muromegalovirus/fisiologia
Proteínas Virais/metabolismo
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Sobrevivência Celular
Seres Humanos
Camundongos
Vírus do Molusco Contagioso/genética
Vírus do Molusco Contagioso/imunologia
Muromegalovirus/genética
Muromegalovirus/imunologia
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Proteínas Virais/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Apoptosis Regulatory Proteins); 0 (Immunologic Factors); 0 (Recombinant Proteins); 0 (Viral Proteins)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:160826
[Lr] Data última revisão:
160826
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160101
[St] Status:MEDLINE
[do] DOI:10.1128/JVI.02729-15


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[PMID]:26584708
[Ti] Título:Patient Perspectives: Molluscum Contagiosum.
[So] Source:Pediatr Dermatol;32(6):e326-7, 2015 Nov-Dec.
[Is] ISSN:1525-1470
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Antivirais/uso terapêutico
Crioterapia/métodos
Molusco Contagioso/diagnóstico
Molusco Contagioso/terapia
Vírus do Molusco Contagioso/isolamento & purificação
Educação de Pacientes como Assunto/métodos
[Mh] Termos MeSH secundário: Administração Oral
Administração Tópica
Adolescente
Aminoquinolinas/uso terapêutico
Criança
Doença Crônica
Feminino
Seres Humanos
Disseminação de Informação/métodos
Masculino
Prognóstico
Retinoides/uso terapêutico
Índice de Gravidade de Doença
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Aminoquinolines); 0 (Antiviral Agents); 0 (Retinoids); P1QW714R7M (imiquimod)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:161126
[Lr] Data última revisão:
161126
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151121
[St] Status:MEDLINE
[do] DOI:10.1111/pde.12752



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