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[PMID]:28449719
[Au] Autor:Bongard N; Lapuente D; Windmann S; Dittmer U; Tenbusch M; Bayer W
[Ad] Endereço:Institute for Virology, University Hospital Essen, University Duisburg-Essen, Virchowstr. 179, 45147, Essen, Germany.
[Ti] Título:Interference of retroviral envelope with vaccine-induced CD8 T cell responses is relieved by co-administration of cytokine-encoding vectors.
[So] Source:Retrovirology;14(1):28, 2017 Apr 27.
[Is] ISSN:1742-4690
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Retroviral envelope (Env) proteins are known to exhibit immunosuppressive properties, which become apparent not only in retroviral infections, but also in gene-based immunizations using retroviral immunogens, where envelope interferes with the induction of CD8 T cell responses towards another, simultaneously or subsequently delivered, immunogen. RESULTS: In the Friend retrovirus mouse model, immunization with a plasmid encoding the Friend murine leukemia virus (F-MuLV) Leader-Gag protein resulted in induction of a strong GagL -specific CD8 T cell response, while the response was completely abrogated by co-immunization with an F-MuLV Env-encoding plasmid. In order to overcome this interference of retroviral envelope, we employed plasmids encoding the cytokines interleukin (IL) 1ß, IL2, IL12, IL15, IL21, IL28A or granulocyte-macrophage colony-stimulating factor (GM-CSF) as genetic adjuvants. Co-application of plasmids encoding IL2, IL12, IL21, IL28A and especially GM-CSF rescued the induction of GagL -specific CD8 T cells in mice vaccinated with FV Leader-Gag and Env. Mice that were immunized with plasmids encoding Leader-Gag and Env and the cytokines IL1ß, IL12, IL15, IL28A or GM-CSF, but not Leader-Gag and Env without any cytokine, showed significantly reduced viral loads upon a high-dose Friend virus challenge infection. CONCLUSIONS: Our data demonstrate the potency of cytokine-encoding vectors as adjuvants and immune modulators in composite vaccines for anti-retroviral immunization.
[Mh] Termos MeSH primário: Linfócitos T CD8-Positivos/imunologia
Citocinas/genética
Vírus da Leucemia Murina de Friend/imunologia
Vacinas de DNA/imunologia
Proteínas do Envelope Viral/imunologia
Vacinas Virais/imunologia
[Mh] Termos MeSH secundário: Adjuvantes Imunológicos
Animais
Citocinas/imunologia
Feminino
Vírus da Leucemia Murina de Friend/genética
Produtos do Gene gag/genética
Produtos do Gene gag/imunologia
Vetores Genéticos
Imunização
Imunomodulação
Interleucina-15/genética
Interleucina-15/imunologia
Interleucina-2/genética
Interleucina-2/imunologia
Camundongos
Camundongos Endogâmicos BALB C
Plasmídeos
Infecções por Retroviridae/imunologia
Vacinas de DNA/administração & dosagem
Proteínas do Envelope Viral/genética
Proteínas do Envelope Viral/metabolismo
Carga Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adjuvants, Immunologic); 0 (Cytokines); 0 (Gene Products, gag); 0 (Interleukin-15); 0 (Interleukin-2); 0 (Vaccines, DNA); 0 (Viral Envelope Proteins); 0 (Viral Vaccines)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1186/s12977-017-0352-7


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[PMID]:28986292
[Au] Autor:Scicluna MT; Autorino GL; Nogarol C; Ricci I; Frontoso R; Rosone F; Nardini R
[Ad] Endereço:Istituto Zooprofilattico Sperimentale del Lazio e della Toscana "M. Aleandri", Via Appia Nuova 1411, 00178 Rome, Italy.
[Ti] Título:Validation of an indirect ELISA employing a chimeric recombinant gag and env peptide for the serological diagnosis of equine infectious anemia.
[So] Source:J Virol Methods;251:111-117, 2018 Jan.
[Is] ISSN:1879-0984
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The National Reference Center for equine infectious anemia (EIA) validated a commercial ELISA (Eradikit EIAV Indirect ELISA, In3diagnostic , Turin, Italy) employing a chimeric recombinant gag and env peptide for the detection of EIA virus antibodies, following the guidelines of the World Organization for Animal Health. The validation parameters evaluated were: analytical sensitivity (Se) and specificity (Sp); diagnostic Se and Sp; precision, based on repeatability and reproducibility through the estimation of the standard deviation (SD) and the coefficient of variation (CV); accuracy, estimated from a multiple K and relative Sp and Se with respect to those of the agar gel immunodiffusion test (AGIDT). Positive and negative predictive values were also defined. The assay showed a high specificity and a limit of detection of 1.43 log major than AGIDT. Diagnostic Se was 100% and Sp was 99.3%, while SD values ranged from 1.58 to 5.01 with a CV between 2.8% and 28.8%. Multiple K was 0.98 and relative Se and Sp were respectively 99.1% and 100%. The assay proved to be robust and to possess a high sensitivity in detecting first antibodies produced at onset of infection as well as high analytic and diagnostic Se and Sp values, confirming it as a serological assay fit for purpose within EIA surveillance programs.
[Mh] Termos MeSH primário: Anticorpos Antivirais/sangue
Antígenos Virais/imunologia
Ensaio de Imunoadsorção Enzimática/métodos
Anemia Infecciosa Equina/diagnóstico
Vírus da Anemia Infecciosa Equina/imunologia
Proteínas Recombinantes/imunologia
Testes Sorológicos/métodos
[Mh] Termos MeSH secundário: Animais
Antígenos Virais/genética
Produtos do Gene env/genética
Produtos do Gene env/imunologia
Produtos do Gene gag/genética
Produtos do Gene gag/imunologia
Cavalos
Valor Preditivo dos Testes
Proteínas Recombinantes/genética
Reprodutibilidade dos Testes
Sensibilidade e Especificidade
[Pt] Tipo de publicação:JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Antibodies, Viral); 0 (Antigens, Viral); 0 (Gene Products, env); 0 (Gene Products, gag); 0 (Recombinant Proteins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180201
[Lr] Data última revisão:
180201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171008
[St] Status:MEDLINE


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[PMID]:28715971
[Au] Autor:Lippincott-Schwartz J; Freed EO; van Engelenburg SB
[Ad] Endereço:Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia 20147.
[Ti] Título:A Consensus View of ESCRT-Mediated Human Immunodeficiency Virus Type 1 Abscission.
[So] Source:Annu Rev Virol;4(1):309-325, 2017 Sep 29.
[Is] ISSN:2327-0578
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The strong dependence of retroviruses, such as human immunodeficiency virus type 1 (HIV-1), on host cell factors is no more apparent than when the endosomal sorting complex required for transport (ESCRT) machinery is purposely disengaged. The resulting potent inhibition of retrovirus release underscores the importance of understanding fundamental structure-function relationships at the ESCRT-HIV-1 interface. Recent studies utilizing advanced imaging technologies have helped clarify these relationships, overcoming hurdles to provide a range of potential models for ESCRT-mediated virus abscission. Here, we discuss these models in the context of prior work detailing ESCRT machinery and the HIV-1 release process. To provide a template for further refinement, we propose a new working model for ESCRT-mediated HIV-1 release that reconciles disparate and seemingly conflicting studies.
[Mh] Termos MeSH primário: Complexos Endossomais de Distribuição Requeridos para Transporte/fisiologia
HIV-1/metabolismo
Liberação de Vírus
[Mh] Termos MeSH secundário: Transporte Biológico
Linhagem Celular
Produtos do Gene gag/genética
Produtos do Gene gag/metabolismo
Seres Humanos
Membranas/metabolismo
Modelos Biológicos
Transporte Proteico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Endosomal Sorting Complexes Required for Transport); 0 (Gene Products, gag)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170719
[St] Status:MEDLINE
[do] DOI:10.1146/annurev-virology-101416-041840


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[PMID]:28667757
[Au] Autor:Cervera L; González-Domínguez I; Segura MM; Gòdia F
[Ad] Endereço:Grup d'Enginyeria Cellular i Bioprocés, Escola d'Enginyeria, Universitat Autònoma de Barcelona, Campus de Bellaterra, Cerdanyola del Vallès, 08193, Barcelona, Spain.
[Ti] Título:Intracellular characterization of Gag VLP production by transient transfection of HEK 293 cells.
[So] Source:Biotechnol Bioeng;114(11):2507-2517, 2017 Nov.
[Is] ISSN:1097-0290
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Transient transfection is a fast, flexible, and cost-effective approach to produce biological products. Despite the continued interest in transient transfection, little is known regarding the transfection process at the intracellular level, particularly for complex products, such as virus-like particles (VLPs). The kinetics of PEI-mediated transfection following an established in-house protocol is reported in this work with the aim of characterizing and understanding the complete process leading to VLP generation and identifying important events driving process improvement. For this purpose, DNA/PEI polyplexes' internalization in cells was tracked using Cy3 DNA staining. The production of a fluorescently labeled Gag polyprotein (a Gag-GFP fusion construct that forms fluorescent Gag-VLPs) was monitored by flow cytometry and confocal microscopy, and the VLP concentration in supernatants was measured by fluorometry. DNA/PEI polyplexes interact with the cell membrane immediately after polyplex addition to the cell culture. A linear increase in the number of cells expressing the protein is observed during the first 60 min of contact between the cells and polyplexes. No additional improvement in the number of cells expressing the protein (up to 60%) or VLP production (up to 1 × 10 VLPs/mL) is observed with additional contact time between the cells and polyplexes. Polyplexes can be detected in the cytoplasm of transfected cells as early as 1.5 h post-transfection (hpt) and reach the nucleus approximately 4 hpt. GFP fluorescence is observed homogeneously in the cytoplasm of transfected cells 24 hpt, but generalized VLP budding is not observed by microscopy until 48 hpt. Although all cells have internalized a polyplex soon after transfection, only a fraction of cells (60%) express the fluorescent Gag protein. VLP production kinetics was also studied. Fluorescence in the supernatant (enveloped VLPs) is 40% less than total fluorescence, supernatant plus pellet (total Gag-GFP), indicating that there is a fraction of Gag that remains inside the cells. The maximum VLP concentration in the cell culture supernatant with cell viability >89% was observed at 72 hpt, which was determined to be the optimal harvest time. Biotechnol. Bioeng. 2017;114: 2507-2517. © 2017 Wiley Periodicals, Inc.
[Mh] Termos MeSH primário: Produtos do Gene gag/genética
Engenharia de Proteínas/métodos
Proteínas Recombinantes/biossíntese
Transfecção/métodos
Vacinas de Partículas Semelhantes a Vírus/biossíntese
[Mh] Termos MeSH secundário: Células HEK293
Seres Humanos
Proteínas Recombinantes/genética
Vacinas de Partículas Semelhantes a Vírus/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Gene Products, gag); 0 (Recombinant Proteins); 0 (Vaccines, Virus-Like Particle)
[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:170702
[St] Status:MEDLINE
[do] DOI:10.1002/bit.26367


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[PMID]:28475623
[Au] Autor:Ovejero CA; Affranchino JL; González SA
[Ad] Endereço:Laboratorio de Virología, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)-Universidad de Belgrano (UB), Buenos Aires, Argentina.
[Ti] Título:Analysis of the functional compatibility of SIV capsid sequences in the context of the FIV gag precursor.
[So] Source:PLoS One;12(5):e0177297, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The formation of immature lentiviral particles is dependent on the multimerization of the Gag polyprotein at the plasma membrane of the infected cells. One key player in the virus assembly process is the capsid (CA) domain of Gag, which establishes the protein-protein interactions that give rise to the hexagonal lattice of Gag molecules in the immature virion. To gain a better understanding of the functional equivalence between the CA proteins of simian and feline immunodeficiency viruses (SIV and FIV, respectively), we generated a series of chimeric FIV Gag proteins in which the CA-coding region was partially or totally replaced by its SIV counterpart. All the FIV Gag chimeras were found to be assembly-defective; however, all of them are able to interact with wild-type SIV Gag and be recruited into extracellular virus-like particles, regardless of the SIV CA sequences present in the chimeric FIV Gag. The results presented here markedly contrast with our previous findings showing that chimeric SIVs carrying FIV CA-derived sequences are assembly-competent. Overall, our data support the notion that although the SIV and FIV CA proteins share 51% amino acid sequence similarity and exhibit a similar organization, i.e., an N-terminal domain joined by a flexible linker to a C-terminal domain, their functional exchange between these different lentiviruses is strictly dependent on the context of the recipient Gag precursor.
[Mh] Termos MeSH primário: Capsídeo/metabolismo
Produtos do Gene gag/metabolismo
Vírus da Imunodeficiência Felina/metabolismo
Vírus da Imunodeficiência Símia/metabolismo
[Mh] Termos MeSH secundário: Animais
Células COS
Proteínas do Capsídeo/metabolismo
Cercopithecus aethiops
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Capsid Proteins); 0 (Gene Products, gag)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170911
[Lr] Data última revisão:
170911
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170506
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0177297


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[PMID]:28394277
[Au] Autor:Blaszczyk L; Biesiada M; Saha A; Garfinkel DJ; Purzycka KJ
[Ad] Endereço:Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan 61-704, Poland. blaszcz@ibch.poznan.pl.
[Ti] Título:Structure of Ty1 Internally Initiated RNA Influences Restriction Factor Expression.
[So] Source:Viruses;9(4), 2017 Apr 10.
[Is] ISSN:1999-4915
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:The long-terminal repeat retrotransposon Ty1 is the most abundant mobile genetic element in many isolates. Ty1 retrotransposons contribute to the genetic diversity of host cells, but they can also act as an insertional mutagen and cause genetic instability. Interestingly, retrotransposition occurs at a low level despite a high level of Ty1 RNA, even though lacks the intrinsic defense mechanisms that other eukaryotes use to prevent transposon movement. p22 is a recently discovered Ty1 protein that inhibits retrotransposition in a dose-dependent manner. p22 is a truncated form of Gag encoded by internally initiated Ty1i RNA that contains two closely-spaced AUG codons. Mutations of either AUG codon compromise p22 translation. We found that both AUG codons were utilized and that translation efficiency depended on the Ty1i RNA structure. Structural features that stimulated p22 translation were context dependent and present only in Ty1i RNA. Destabilization of the 5' untranslated region (5' UTR) of Ty1i RNA decreased the p22 level, both in vitro and in vivo. Our data suggest that protein factors such as Gag could contribute to the stability and translational activity of Ty1i RNA through specific interactions with structural motifs in the RNA.
[Mh] Termos MeSH primário: Produtos do Gene gag/metabolismo
Biossíntese de Proteínas
RNA Fúngico/metabolismo
Recombinação Genética
Retroelementos
Saccharomyces cerevisiae/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Gene Products, gag); 0 (RNA, Fungal); 0 (Retroelements)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170927
[Lr] Data última revisão:
170927
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170411
[St] Status:MEDLINE


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[PMID]:28342872
[Au] Autor:Wang J; Wen S; Zhao R; Qi J; Liu Z; Li W; An J; Wood C; Wang Y
[Ad] Endereço:TEDA Institute of Biological Sciences and Biotechnology, Nankai University, 23 Hongda Street, TEDA, Tianjin 300457, China; Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, 23 Hongda Street, TEDA, Tianjin 300457, China; Tianjin Key Laboratory of Microbial Functional Gen
[Ti] Título:Covalent conjugation of the equine infectious anemia virus Gag with SUMO.
[So] Source:Biochem Biophys Res Commun;486(3):712-719, 2017 May 06.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The conjugation of small ubiquitin-like modifier (SUMO) to the target protein, namely, SUMOylation, is involved in the regulation of many important biological events including host-pathogen interaction. Some viruses have evolved to exploit the host SUMOylation machinery to modify their own protein. Retroviral Gag protein plays critical roles in the viral life cycle. The HIV-1 p6 and the Moloney murine leukemia virus CA have been reported to be conjugated with SUMO. In this study, we report for the first time, to our knowledge, the covalent conjugation of equine infectious anemia virus (EIAV) Gag with SUMO. The C-terminal p9 domain of Gag is a main target for SUMOylation and SUMO is attached to multiple sites of p9, including K30 whose mutation abolished p9 SUMOylation completely. The SUMOylation of p9, but not the p9-K30 mutant, was also detected in equine fibroblastic cells ATCC CCL-57™. Ubc9 and its C93 residue are indispensable for the SUMOylation of p9. Using confocal microscopy, it is found that EIAV Gag localizes primarily, if not exclusively, in the cytoplasm of the cell and the co-localization of EIAV Gag with Ubc9 was observed. Our findings that EIAV Gag is SUMOylated at p9-K30, together with previous findings on the defects of p9-K30 mutant in viral DNA translocation from cytoplasm to the nucleus, suggests that SUMOylation of Gag may be involved in such functions.
[Mh] Termos MeSH primário: Produtos do Gene gag/genética
Vírus da Anemia Infecciosa Equina/genética
Lisina/metabolismo
Proteína SUMO-1/genética
Enzimas de Conjugação de Ubiquitina/genética
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Linhagem Celular
Escherichia coli/genética
Escherichia coli/metabolismo
Fibroblastos/metabolismo
Fibroblastos/virologia
Regulação da Expressão Gênica
Produtos do Gene gag/metabolismo
Células HEK293
Cavalos
Interações Hospedeiro-Patógeno
Seres Humanos
Vírus da Anemia Infecciosa Equina/metabolismo
Mutação
Domínios Proteicos
Proteína SUMO-1/metabolismo
Transdução de Sinais
Sumoilação
Enzimas de Conjugação de Ubiquitina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Gene Products, gag); 0 (SUMO-1 Protein); EC 2.3.2.23 (Ubiquitin-Conjugating Enzymes); EC 6.3.2.- (ubiquitin-conjugating enzyme UBC9); K3Z4F929H6 (Lysine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170602
[Lr] Data última revisão:
170602
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170327
[St] Status:MEDLINE


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[PMID]:28333940
[Au] Autor:Lu W; Wan Y; Ma F; Johnson RP; Li Q
[Ad] Endereço:School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America.
[Ti] Título:Distinct transcriptome profiles of Gag-specific CD8+ T cells temporally correlated with the protection elicited by SIVΔnef live attenuated vaccine.
[So] Source:PLoS One;12(3):e0173929, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The live attenuated vaccine (LAV) SIVmac239Δnef (SIVΔnef) confers the best protection among all the vaccine modalities tested in rhesus macaque model of HIV-1 infection. This vaccine has a unique feature of time-dependent protection: macaques are not protected at 3-5 weeks post vaccination (WPV), whereas immune protection emerges between 15 and 20 WPV. Although the exact mechanisms of the time-dependent protection remain incompletely understood, studies suggested that both cellular and humoral immunities contribute to this time-dependent protection. To further elucidate the mechanisms of protection induced by SIVΔnef, we longitudinally compared the global gene expression profiles of SIV Gag-CM9+ CD8+ (Gag-specific CD8+) T cells from peripheral blood of Mamu-A*01+ rhesus macaques at 3 and 20 WPV using rhesus microarray. We found that gene expression profiles of Gag-specific CD8+ T cells at 20 WPV are qualitatively different from those at 3 WPV. At 20 WPV, the most significant transcriptional changes of Gag-specific CD8+ T cells were genes involved in TCR signaling, differentiation and maturation toward central memory cells, with increased expression of CCR7, TCRα, TCRß, CD28 and decreased expression of CTLA-4, IFN-γ, RANTES, granzyme A and B. Our study suggests that a higher quality of SIV-specific CD8+ T cells elicited by SIVΔnef over time contributes to the maturation of time-dependent protection.
[Mh] Termos MeSH primário: Linfócitos T CD8-Positivos/metabolismo
Produtos do Gene gag/imunologia
Vacinas contra a SAIDS/imunologia
Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle
Vírus da Imunodeficiência Símia/imunologia
Transcriptoma
[Mh] Termos MeSH secundário: Animais
Linfócitos T CD8-Positivos/imunologia
Produtos do Gene nef/imunologia
Imunidade Celular
Imunidade Humoral
Macaca mulatta/imunologia
Macaca mulatta/virologia
Masculino
Síndrome de Imunodeficiência Adquirida dos Símios/imunologia
Fatores de Tempo
Vacinas Atenuadas/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Gene Products, gag); 0 (Gene Products, nef); 0 (SAIDS Vaccines); 0 (Vaccines, Attenuated)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170825
[Lr] Data última revisão:
170825
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170324
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0173929


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[PMID]:28130554
[Au] Autor:Kowalczyk MJ; Teresiak-Mikolajczak E; Danczak-Pazdrowska A; Zaba R; Adamski Z; Osmola-Mankowska A
[Ad] Endereço:Department of Dermatology and Venereology, Psoriasis and Novel Therapies in Dermatology Unit, Poznan University of Medical Sciences, Poznan, Poland.
[Ti] Título:Effects of UVA1 Phototherapy on Expression of Human Endogenous Retroviral Sequence (HERV)-K10 gag in Morphea: A Preliminary Study.
[So] Source:Med Sci Monit;23:505-512, 2017 Jan 28.
[Is] ISSN:1643-3750
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND Morphea, also known as localized scleroderma, is a rare autoimmune connective tissue disease characterized by skin fibrosis. UVA1 phototherapy is an important asset in the reduction of clinical manifestations in morphea. There are studies claiming that UV light modulates the expression of some human endogenous retroviral sequences. The aim of this study was to determine if the expression of HERV-K10 gag element is lowered by UVA1 phototherapy in morphea, a disease in which such irradiation has a soothing effect. MATERIAL AND METHODS The expression levels of the HERV-K10 gag were assessed by real-time PCR (polymerase chain reaction) in peripheral blood mononuclear cells (PBMC) and skin-punch biopsies of healthy volunteers and 9 morphea patients before and after phototherapy. Additionally, correlations between the HERV-K10 gag expression and age, disease duration, the Localized Scleroderma Skin Severity Index (LoSSI), and antinuclear antibody (ANA) titers were assessed. RESULTS In PBMC, HERV-K10 gag mRNA was significantly elevated after UVA1 phototherapy compared to healthy controls. Most of the patients responded with an increased expression level of this sequence. However, we found no statistical evidence at this point that phototherapy indeed has an effect on the HERV-K10 gag expression (there were no statistical differences in PBMC of morphea patients before and after phototherapy). Similarly, there was no statistically relevant effect of the UVA1 on the expression of HERV-K10 gag in skin. CONCLUSIONS At this point, the effect of UVA1 phototherapy on the expression of HERV-K10 gag cannot be statistically confirmed.
[Mh] Termos MeSH primário: Retrovirus Endógenos/efeitos da radiação
Produtos do Gene gag/biossíntese
Infecções por Retroviridae/terapia
Esclerodermia Localizada/terapia
Terapia Ultravioleta/métodos
[Mh] Termos MeSH secundário: Adulto
Idoso
Estudos de Casos e Controles
Retrovirus Endógenos/genética
Retrovirus Endógenos/metabolismo
Feminino
Produtos do Gene gag/genética
Produtos do Gene gag/metabolismo
Seres Humanos
Leucócitos Mononucleares/efeitos da radiação
Masculino
Meia-Idade
RNA Mensageiro/genética
Reação em Cadeia da Polimerase em Tempo Real
Infecções por Retroviridae/sangue
Infecções por Retroviridae/patologia
Infecções por Retroviridae/virologia
Esclerodermia Localizada/sangue
Esclerodermia Localizada/patologia
Esclerodermia Localizada/virologia
Raios Ultravioleta
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Gene Products, gag); 0 (HERV-K10gag protein, K10 retrovirus); 0 (RNA, Messenger)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170608
[Lr] Data última revisão:
170608
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170129
[St] Status:MEDLINE


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[PMID]:28083937
[Au] Autor:Bashratyan R; Regn D; Rahman MJ; Marquardt K; Fink E; Hu WY; Elder JH; Binley J; Sherman LA; Dai YD
[Ad] Endereço:Department of Immunology & Microbial Science, The Scripps Research Institute, La Jolla, CA, USA.
[Ti] Título:Type 1 diabetes pathogenesis is modulated by spontaneous autoimmune responses to endogenous retrovirus antigens in NOD mice.
[So] Source:Eur J Immunol;47(3):575-584, 2017 Mar.
[Is] ISSN:1521-4141
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Secreted microvesicles (MVs) are potent inflammatory triggers that stimulate autoreactive B and T cells, causing Type 1 Diabetes in non-obese diabetic (NOD) mice. Proteomic analysis of purified MVs released from islet cells detected the presence of endogenous retrovirus (ERV) antigens, including Env and Gag sequences similar to the well-characterized murine leukemia retroviruses. This raises the possibility that ERV antigens may be expressed in the pancreatic islets via MV secretion. Using virus-like particles produced by co-expressing ERV Env and Gag antigens, and a recombinant gp70 Env protein, we demonstrated that NOD but not diabetes-resistant mice developed anti-Env autoantibodies that increase in titer as disease progresses. A lentiviral-based RNA interference knockdown of Gag revealed that Gag contributes to the MV-induced T-cell response, whose diabetogenic function can be demonstrated via cell-transfer into immune-deficient mice. Finally, we observed that Gag and Env are expressed in NOD islet-derived primary mesenchymal stem cells (MSCs). However, MSCs derived from the islets of diabetes-resistant mice do not express the antigens. Taken together, abnormal ERV activation and secretion of MVs may induce anti-retroviral responses to trigger autoimmunity.
[Mh] Termos MeSH primário: Micropartículas Derivadas de Células/metabolismo
Diabetes Mellitus Tipo 1/imunologia
Retrovirus Endógenos/imunologia
Produtos do Gene env/metabolismo
Produtos do Gene gag/metabolismo
Ilhotas Pancreáticas/imunologia
Células Mesenquimais Estromais/metabolismo
Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Transferência Adotiva
Animais
Autoanticorpos/sangue
Autoimunidade
Micropartículas Derivadas de Células/imunologia
Células Cultivadas
Feminino
Produtos do Gene env/genética
Produtos do Gene gag/genética
Seres Humanos
Ilhotas Pancreáticas/metabolismo
Ativação Linfocitária
Células Mesenquimais Estromais/imunologia
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Endogâmicos NOD
RNA Interferente Pequeno/genética
Linfócitos T/transplante
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Autoantibodies); 0 (Gene Products, env); 0 (Gene Products, gag); 0 (RNA, Small Interfering)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170718
[Lr] Data última revisão:
170718
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170114
[St] Status:MEDLINE
[do] DOI:10.1002/eji.201646755



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