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[PMID]:29030319
[Au] Autor:Dutta S; Celestine MJ; Khanal S; Huddleston A; Simms C; Arca JF; Mitra A; Heller L; Kraj PJ; Ledizet M; Anderson JF; Neelakanta G; Holder AA; Sultana H
[Ad] Endereço:Department of Biological Sciences, Old Dominion University, Norfolk, VA, USA.
[Ti] Título:Coordination of different ligands to copper(II) and cobalt(III) metal centers enhances Zika virus and dengue virus loads in both arthropod cells and human keratinocytes.
[So] Source:Biochim Biophys Acta;1862(1):40-50, 2018 01.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Trace elements such as copper and cobalt have been associated with virus-host interactions. However, studies to show the effect of conjugation of copper(II) or cobalt(III) metal centers to thiosemicarbazone ligand(s) derived from either food additives or mosquito repellent such as 2-acetylethiazole or citral, respectively, on Zika virus (ZIKV) or dengue virus (serotype 2; DENV2) infections have not been explored. In this study, we show that four compounds comprising of thiosemicarbazone ligand derived from 2-acetylethiazole viz., (E)-N-ethyl-2-[1-(thiazol-2-yl)ethylidene]hydrazinecarbothioamide (acetylethTSC) (compound 1), a copper(II) complex with acetylethTSC as a ligand (compound 2), a thiosemicarbazone ligand-derived from citral (compound 3) and a cobalt(III) complex with a citral-thiosemicarbazone ligand (compound 4) increased DENV2 and ZIKV replication in both mosquito C6/36 cells and human keratinocytes (HaCaT cells). Treatment of both cell lines with compounds 2 or 4 showed increased dengue viral titers at all three tested doses. Enhanced dengue viral plaque formation was also noted at the tested dose of 100µM, suggesting higher production of infectious viral particles. Treatment with the compounds 2 or 4 enhanced ZIKV and DENV2 RNA levels in HeLa cell line and primary cultures of mouse bone marrow derived dendritic cells. Also, pre- or post treatments with conjugated compounds 2 or 4 showed higher loads of ZIKV or DENV2 envelope (E) protein in HaCaT cells. No changes in loads of E-protein were found in ZIKV-infected C6/36 cells, when compounds were treated after infection. In addition, we tested bis(1,10-phenanthroline)copper(II) chloride ([Cu(phen) ]Cl , (compound 5) and tris(1,10-phenanthroline)cobalt(III) chloride ([Co(phen) ]Cl , (compound 6) that also showed enhanced DENV2 loads. Also, we found that copper(II) chloride dehydrate (CuCl ·2H O) or cobalt(II) chloride hexahydrate (CoCl ·6H O) alone had no effects as "free" cations. Taken together, these findings suggest that use of Cu(II) or Co(III) conjugation to organic compounds, in insect repellents and/or food additives could enhance DENV2/ZIKV loads in human cells and perhaps induce pathogenesis in infected individuals or individuals pre-exposed to such conjugated complexes. IMPORTANCE: Mosquito-borne diseases are of great concern to the mankind. Use of chemicals/repellents against mosquito bites and transmission of microbes has been the topic of interest for many years. Here, we show that thiosemicarbazone ligand(s) derived from 2-acetylethiazole or citral or 1,10-phenanthroline upon conjugation with copper(II) or cobalt(III) metal centers enhances dengue virus (serotype 2; DENV2) and/or Zika virus (ZIKV) infections in mosquito, mouse and human cells. Enhanced ZIKV/DENV2 capsid mRNA or envelope protein loads were evident in mosquito cells and human keratinocytes, when treated with compounds before/after infections. Also, treatment with copper(II) or cobalt(III) conjugated compounds increased viral titers and number of plaque formations. These studies suggest that conjugation of compounds in repellents/essential oils/natural products/food additives with copper(II) or cobalt(III) metal centers may not be safe, especially in tropical and subtropical places, where several dengue infection cases and deaths are reported annually or in places with increased ZIKV caused microcephaly.
[Mh] Termos MeSH primário: Cobalto
Complexos de Coordenação
Cobre
Vírus da Dengue/metabolismo
Queratinócitos/virologia
Carga Viral/efeitos dos fármacos
Zika virus/metabolismo
[Mh] Termos MeSH secundário: Animais
Cercopithecus aethiops
Cobalto/química
Cobalto/farmacologia
Complexos de Coordenação/química
Complexos de Coordenação/farmacologia
Cobre/química
Cobre/farmacologia
Culicidae
Células HeLa
Seres Humanos
Queratinócitos/metabolismo
Queratinócitos/patologia
Células Vero
Proteínas do Envelope Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Coordination Complexes); 0 (Viral Envelope Proteins); 3G0H8C9362 (Cobalt); 789U1901C5 (Copper)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171015
[St] Status:MEDLINE


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[PMID]:28456782
[Au] Autor:Lee CH; Nishikawa T; Kaneda Y
[Ad] Endereço:Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan.
[Ti] Título:Salmonella mediated the hemagglutinating virus of Japan-envelope transfer suppresses tumor growth.
[So] Source:Oncotarget;8(21):35048-35060, 2017 May 23.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Salmonella can target to tumor microenvironments after systemic treatment. The hemagglutinating virus of Japan-envelope (HVJ-E) induced apoptosis in tumor cells without toxicity in normal cells. Current HVJ-E therapeutic strategies, aimed at using HVJ-E for intratumor treatment, have shown great promise in animal models but have achieved only limited systemic treatment. The purpose of this study was to investigate the modulation of the anti-tumor efficiency of HVJ-E by coating the particles with poly (allylamine hydrochloride) (PAH), designated as P-HVJ-E. Treatment with P-HVJ-E resulted in decreased hemagglutinating activity and maintained tumor cell-selective apoptosis and anti-tumor immunity. The use of Salmonella as a coating for P-HVJ-E (PHS) enhanced the antitumor activity and maintained the tumor-targeting activity. Treatment with PHS resulted in delayed tumor growth in tumor-bearing mice. Furthermore, a Western blot assay of the tumors revealed that HVJ-E targeted to the tumor after systemic treatment with PHS. These results indicate that Salmonella coating viral particles may provide a new approach for tumor therapy.
[Mh] Termos MeSH primário: Neoplasias Experimentais/tratamento farmacológico
Poliaminas/química
Salmonella/fisiologia
Vírus Sendai/metabolismo
Proteínas do Envelope Viral/administração & dosagem
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Seres Humanos
Camundongos
Microambiente Tumoral
Proteínas do Envelope Viral/química
Proteínas do Envelope Viral/farmacologia
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Polyamines); 0 (Viral Envelope Proteins); 30551-89-4 (polyallylamine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.17037


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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]:29338045
[Au] Autor:Kim AR; Lee DH; Lee SH; Rubino I; Choi HJ; Quan FS
[Ad] Endereço:Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Korea.
[Ti] Título:Protection induced by virus-like particle vaccine containing tandem repeat gene of respiratory syncytial virus G protein.
[So] Source:PLoS One;13(1):e0191277, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract illness in infants, young children and the elderly. However, there is no licensed vaccine available against RSV infection. In this study, we generated virus-like particle (VLP) vaccine and investigated the vaccine efficacy in a mouse model. For VLP vaccines, tandem gene (1-780 bp) for V1 VLPs and tandem repeat gene (repeated 450-780 bp) for V5 VLPs were constructed in pFastBacTM vectors, respectively. Influenza matrix protein 1 (M1) was used as a core protein in the VLPs. Notably, upon challenge infection, significantly lower virus loads were measured in the lung of mice immunized with V1 or V5 VLPs compared to those of naïve mice and formalin-inactivated RSV immunized control mice. In particular, V5 VLPs immunization showed significantly lower virus titers than V1 VLPs immunization. Furthermore, V5 VLPs immunization elicited increased memory B cells responses in the spleen. These results indicated that V5 VLP vaccine containing tandem repeat gene protein provided better protection than V1 VLPs with significantly decreased inflammation in the lungs. Thus, V5 VLPs could be a potential vaccine candidate against RSV.
[Mh] Termos MeSH primário: Infecções por Vírus Respiratório Sincicial/prevenção & controle
Vacinas contra Vírus Sincicial Respiratório/farmacologia
Vírus Sincicial Respiratório Humano/genética
Vírus Sincicial Respiratório Humano/imunologia
Vacinas de Partículas Semelhantes a Vírus/farmacologia
Proteínas do Envelope Viral/genética
Proteínas do Envelope Viral/imunologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Antivirais/sangue
Modelos Animais de Doenças
Feminino
Genes Virais
Seres Humanos
Pulmão/imunologia
Pulmão/patologia
Pulmão/virologia
Camundongos
Camundongos Endogâmicos BALB C
Infecções por Vírus Respiratório Sincicial/imunologia
Infecções por Vírus Respiratório Sincicial/virologia
Vacinas contra Vírus Sincicial Respiratório/genética
Sequências de Repetição em Tandem
Vacinas de Partículas Semelhantes a Vírus/genética
Carga Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies, Viral); 0 (Respiratory Syncytial Virus Vaccines); 0 (Vaccines, Virus-Like Particle); 0 (Viral Envelope Proteins); 0 (attachment protein G)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180117
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191277


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[PMID]:28461071
[Au] Autor:Langsjoen RM; Auguste AJ; Rossi SL; Roundy CM; Penate HN; Kastis M; Schnizlein MK; Le KC; Haller SL; Chen R; Watowich SJ; Weaver SC
[Ad] Endereço:Institute for Translational Science, University of Texas Medical Branch, Galveston, TX, USA; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.
[Ti] Título:Host oxidative folding pathways offer novel anti-chikungunya virus drug targets with broad spectrum potential.
[So] Source:Antiviral Res;143:246-251, 2017 07.
[Is] ISSN:1872-9096
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Alphaviruses require conserved cysteine residues for proper folding and assembly of the E1 and E2 envelope glycoproteins, and likely depend on host protein disulfide isomerase-family enzymes (PDI) to aid in facilitating disulfide bond formation and isomerization in these proteins. Here, we show that in human HEK293 cells, commercially available inhibitors of PDI or modulators thereof (thioredoxin reductase, TRX-R; endoplasmic reticulum oxidoreductin-1, ERO-1) inhibit the replication of CHIKV chikungunya virus (CHIKV) in vitro in a dose-dependent manner. Further, the TRX-R inhibitor auranofin inhibited Venezuelan equine encephalitis virus and the flavivirus Zika virus replication in vitro, while PDI inhibitor 16F16 reduced replication but demonstrated notable toxicity. 16F16 significantly altered the viral genome: plaque-forming unit (PFU) ratio of CHIKV in vitro without affecting relative intracellular viral RNA quantities and inhibited CHIKV E1-induced cell-cell fusion, suggesting that PDI inhibitors alter progeny virion infectivity through altered envelope function. Auranofin also increased the extracellular genome:PFU ratio but decreased the amount of intracellular CHIKV RNA, suggesting an alternative mechanism of action. Finally, auranofin reduced footpad swelling and viremia in the C57BL/6 murine model of CHIKV infection. Our results suggest that targeting oxidative folding pathways represents a potential new anti-alphavirus therapeutic strategy.
[Mh] Termos MeSH primário: Antivirais/farmacologia
Febre de Chikungunya/virologia
Vírus Chikungunya/efeitos dos fármacos
Vírus Chikungunya/fisiologia
Interações Hospedeiro-Patógeno/fisiologia
[Mh] Termos MeSH secundário: Infecções por Alphavirus/virologia
Animais
Auranofina/antagonistas & inibidores
Febre de Chikungunya/mortalidade
Vírus Chikungunya/patogenicidade
Modelos Animais de Doenças
Vírus da Encefalite Equina Venezuelana/efeitos dos fármacos
Flavivirus/efeitos dos fármacos
Células HEK293
Seres Humanos
Glicoproteínas de Membrana
Camundongos
Camundongos Endogâmicos C57BL
Isomerases de Dissulfetos de Proteínas/farmacologia
Dobramento de Proteína
Tiorredoxina Dissulfeto Redutase/farmacologia
Proteínas do Envelope Viral/metabolismo
Replicação Viral/efeitos dos fármacos
Zika virus/efeitos dos fármacos
Infecção pelo Zika virus/virologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Membrane Glycoproteins); 0 (Viral Envelope Proteins); 3H04W2810V (Auranofin); EC 1.8.1.9 (Thioredoxin-Disulfide Reductase); EC 5.3.4.1 (Protein Disulfide-Isomerases)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


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[PMID]:28457855
[Au] Autor:Tan CW; Sam IC; Chong WL; Lee VS; Chan YF
[Ad] Endereço:Department of Medical Microbiology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: tancw86@gmail.com.
[Ti] Título:Polysulfonate suramin inhibits Zika virus infection.
[So] Source:Antiviral Res;143:186-194, 2017 07.
[Is] ISSN:1872-9096
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Zika virus (ZIKV) is an arthropod-borne flavivirus that causes newborn microcephaly and Guillian-Barré syndrome in adults. No therapeutics are available to treat ZIKV infection or other flaviviruses. In this study, we explored the inhibitory effect of glycosaminoglycans and analogues against ZIKV infection. Highly sulfated heparin, dextran sulfate and suramin significantly inhibited ZIKV infection in Vero cells. De-sulfated heparin analogues lose inhibitory effect, implying that sulfonate groups are critical for viral inhibition. Suramin, an FDA-approved anti-parasitic drug, inhibits ZIKV infection with 3-5 log PFU viral reduction with IC value of ∼2.5-5 µg/ml (1.93 µM-3.85 µM). A time-of-drug-addition study revealed that suramin remains potent even when administrated at 1-24 hpi. Suramin inhibits ZIKV infection by preventing viral adsorption, entry and replication. Molecular dynamics simulation revealed stronger interaction of suramin with ZIKV NS3 helicase than with the envelope protein. Suramin warrants further investigation as a potential antiviral candidate for ZIKV infection. Heparan sulfate (HS) is a cellular attachment receptor for multiple flaviviruses. However, no direct ZIKV-heparin interaction was observed in heparin-binding analysis, and downregulate or removal of cellular HS with sodium chlorate or heparinase I/III did not inhibit ZIKV infection. This indicates that cell surface HS is not utilized by ZIKV as an attachment receptor.
[Mh] Termos MeSH primário: Suramina/antagonistas & inibidores
Infecção pelo Zika virus/prevenção & controle
Zika virus/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Anticorpos Antivirais
Cercopithecus aethiops
Cloratos/farmacologia
DNA Helicases/metabolismo
Sulfato de Dextrana/antagonistas & inibidores
Flavivirus/efeitos dos fármacos
Glicosaminoglicanos/farmacologia
Heparina/análogos & derivados
Heparina/química
Heparina/farmacologia
Heparitina Sulfato/farmacologia
Concentração Inibidora 50
Camundongos
Simulação de Acoplamento Molecular
Simulação de Dinâmica Molecular
RNA Helicases/química
RNA Helicases/efeitos dos fármacos
Serina Endopeptidases/química
Serina Endopeptidases/efeitos dos fármacos
Suramina/administração & dosagem
Células Vero
Proteínas do Envelope Viral/metabolismo
Proteínas não Estruturais Virais/química
Proteínas não Estruturais Virais/efeitos dos fármacos
Internalização do Vírus/efeitos dos fármacos
Replicação Viral/efeitos dos fármacos
Zika virus/fisiologia
Infecção pelo Zika virus/virologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies, Viral); 0 (Chlorates); 0 (Glycosaminoglycans); 0 (NS3 protein, flavivirus); 0 (Viral Envelope Proteins); 0 (Viral Nonstructural Proteins); 6032D45BEM (Suramin); 9005-49-6 (Heparin); 9042-14-2 (Dextran Sulfate); 9050-30-0 (Heparitin Sulfate); EC 3.4.21.- (Serine Endopeptidases); EC 3.6.4.- (DNA Helicases); EC 3.6.4.13 (RNA Helicases); T95DR77GMR (sodium chlorate)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE


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[PMID]:29267278
[Au] Autor:Ricciardi MJ; Magnani DM; Grifoni A; Kwon YC; Gutman MJ; Grubaugh ND; Gangavarapu K; Sharkey M; Silveira CGT; Bailey VK; Pedreño-Lopez N; Gonzalez-Nieto L; Maxwell HS; Domingues A; Martins MA; Pham J; Weiskopf D; Altman J; Kallas EG; Andersen KG; Stevenson M; Lichtenberger P; Choe H; Whitehead SS; Sette A; Watkins DI
[Ad] Endereço:Department of Pathology, University of Miami Miller School of Medicine, Miami, FL, United States of America.
[Ti] Título:Ontogeny of the B- and T-cell response in a primary Zika virus infection of a dengue-naïve individual during the 2016 outbreak in Miami, FL.
[So] Source:PLoS Negl Trop Dis;11(12):e0006000, 2017 12.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Zika virus (ZIKV) is a mosquito-borne flavivirus of significant public health concern. In the summer of 2016, ZIKV was first detected in the contiguous United States. Here we present one of the first cases of a locally acquired ZIKV infection in a dengue-naïve individual. We collected blood from a female with a maculopapular rash at day (D) 5 and D7 post onset of symptoms (POS) and we continued weekly blood draws out to D148 POS. To establish the ontogeny of the immune response against ZIKV, lymphocytes and plasma were analyzed in a longitudinal fashion. The plasmablast response peaked at D7 POS (19.6% of CD19+ B-cells) and was undetectable by D15 POS. ZIKV-specific IgM was present at D5 POS, peaked between D15 and D21 POS, and subsequently decreased. The ZIKV-specific IgG response, however, was not detected until D15 POS and continued to increase after that. Interestingly, even though the patient had never been infected with dengue virus (DENV), cross-reactive IgM and IgG binding against each of the four DENV serotypes could be detected. The highest plasma neutralization activity against ZIKV peaked between D15 and D21 POS, and even though DENV binding antibodies were present in the plasma of the patient, there was neither neutralization nor antibody dependent enhancement (ADE) of DENV. Interestingly, ADE against ZIKV arose at D48 POS and continued until the end of the study. CD4+ and CD8+ T-cells recognized ZIKV-NS2A and ZIKV-E, respectively. The tetramer positive CD8+ T-cell response peaked at D21 POS with elevated levels persisting for months. In summary, this is the first study to establish the timing of the ontogeny of the immune response against ZIKV.
[Mh] Termos MeSH primário: Anticorpos Antivirais/sangue
Linfócitos T CD4-Positivos/imunologia
Linfócitos T CD8-Positivos/imunologia
Imunoglobulina G/sangue
Imunoglobulina M/sangue
Zika virus/imunologia
[Mh] Termos MeSH secundário: Adulto
Anticorpos Antivirais/imunologia
Reações Cruzadas/imunologia
Vírus da Dengue/imunologia
Surtos de Doenças
Exantema/virologia
Feminino
Florida
Seres Humanos
Imunoglobulina G/imunologia
Imunoglobulina M/imunologia
RNA Viral/genética
Proteínas do Envelope Viral/imunologia
Zika virus/genética
Infecção pelo Zika virus/imunologia
Infecção pelo Zika virus/virologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies, Viral); 0 (Immunoglobulin G); 0 (Immunoglobulin M); 0 (RNA, Viral); 0 (Viral Envelope Proteins)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180210
[Lr] Data última revisão:
180210
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171222
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0006000


  8 / 17860 MEDLINE  
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[PMID]:29206240
[Au] Autor:Treat BR; Bidula SM; Ramachandran S; St Leger AJ; Hendricks RL; Kinchington PR
[Ad] Endereço:Molecular Virology and Microbiology Graduate Program, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
[Ti] Título:Influence of an immunodominant herpes simplex virus type 1 CD8+ T cell epitope on the target hierarchy and function of subdominant CD8+ T cells.
[So] Source:PLoS Pathog;13(12):e1006732, 2017 Dec.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Herpes simplex virus type 1 (HSV-1) latency in sensory ganglia such as trigeminal ganglia (TG) is associated with a persistent immune infiltrate that includes effector memory CD8+ T cells that can influence HSV-1 reactivation. In C57BL/6 mice, HSV-1 induces a highly skewed CD8+ T cell repertoire, in which half of CD8+ T cells (gB-CD8s) recognize a single epitope on glycoprotein B (gB498-505), while the remainder (non-gB-CD8s) recognize, in varying proportions, 19 subdominant epitopes on 12 viral proteins. The gB-CD8s remain functional in TG throughout latency, while non-gB-CD8s exhibit varying degrees of functional compromise. To understand how dominance hierarchies relate to CD8+ T cell function during latency, we characterized the TG-associated CD8+ T cells following corneal infection with a recombinant HSV-1 lacking the immunodominant gB498-505 epitope (S1L). S1L induced a numerically equivalent CD8+ T cell infiltrate in the TG that was HSV-specific, but lacked specificity for gB498-505. Instead, there was a general increase of non-gB-CD8s with specific subdominant epitopes arising to codominance. In a latent S1L infection, non-gB-CD8s in the TG showed a hierarchy targeting different epitopes at latency compared to at acute times, and these cells retained an increased functionality at latency. In a latent S1L infection, these non-gB-CD8s also display an equivalent ability to block HSV reactivation in ex vivo ganglionic cultures compared to TG infected with wild type HSV-1. These data indicate that loss of the immunodominant gB498-505 epitope alters the dominance hierarchy and reduces functional compromise of CD8+ T cells specific for subdominant HSV-1 epitopes during viral latency.
[Mh] Termos MeSH primário: Linfócitos T CD8-Positivos/virologia
Herpes Simples/imunologia
Herpesvirus Humano 1/imunologia
Epitopos Imunodominantes/metabolismo
Gânglio Trigeminal/virologia
Proteínas do Envelope Viral/metabolismo
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Animais
Linfócitos T CD8-Positivos/imunologia
Linfócitos T CD8-Positivos/patologia
Linhagem Celular
Células Cultivadas
Cercopithecus aethiops
DNA Recombinante/metabolismo
Infecções Oculares Virais/imunologia
Infecções Oculares Virais/metabolismo
Infecções Oculares Virais/patologia
Infecções Oculares Virais/virologia
Feminino
Deleção de Genes
Herpes Simples/metabolismo
Herpes Simples/patologia
Herpes Simples/virologia
Herpesvirus Humano 1/fisiologia
Camundongos Endogâmicos C57BL
Fragmentos de Peptídeos/química
Fragmentos de Peptídeos/metabolismo
Mutação Puntual
Proteínas Recombinantes de Fusão/química
Proteínas Recombinantes de Fusão/metabolismo
Gânglio Trigeminal/imunologia
Gânglio Trigeminal/patologia
Células Vero
Proteínas do Envelope Viral/química
Proteínas do Envelope Viral/genética
Ativação Viral
Latência Viral
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Recombinant); 0 (Immunodominant Epitopes); 0 (Peptide Fragments); 0 (Recombinant Fusion Proteins); 0 (Viral Envelope Proteins); 0 (glycoprotein B, human herpesvirus 1)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180210
[Lr] Data última revisão:
180210
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171206
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1006732


  9 / 17860 MEDLINE  
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[PMID]:29235980
[Au] Autor:Tucakov AK; Yavuz S; Schürmann EM; Mischler M; Klingebeil A; Meyers G
[Ad] Endereço:Institut für Immunologie, Friedrich-Loeffler-Institut, D-17493 Greifswald-Insel Riems, Germany.
[Ti] Título:Restoration of glycoprotein E dimerization via pseudoreversion partially restores virulence of classical swine fever virus.
[So] Source:J Gen Virol;99(1):86-96, 2018 Jan.
[Is] ISSN:1465-2099
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The classical swine fever virus (CSFV) represents one of the most important pathogens of swine. The CSFV glycoprotein E is an essential structural protein and an important virulence factor. The latter is dependent on the RNase activity of this envelope protein and, most likely, its secretion from the infected cell. A further important feature with regard to its function as a virulence factor is the formation of disulfide-linked E homodimers that are found in virus-infected cells and virions. Mutant CSFV lacking cysteine (Cys) 171, the residue responsible for intermolecular disulfide bond formation, were found to be attenuated in pigs (Tews BA, Schürmann EM, Meyers G. J Virol 2009;83:4823-4834). In the course of an animal experiment with such a dimerization-negative CSFV mutant, viruses were reisolated from pigs that contained a mutation of serine (Ser) 209 to Cys. This mutation restored the ability to form disulphide-linked E homodimers. In transient expression studies E mutants carrying the S209C change were found to form homodimers with about wt efficiency. Also the secretion level of the mutated proteins was equivalent to that of wt E . Virus mutants containing the Cys171Ser/Ser209Cys configuration exhibited wt growth rates and increased virulence when compared with the Cys171Ser mutant. These results provide further support for the connection between CSFV virulence and E dimerization.
[Mh] Termos MeSH primário: Peste Suína Clássica/virologia
Vírus da Febre Suína Clássica/genética
Vírus da Febre Suína Clássica/patogenicidade
Células Epiteliais/virologia
Mutação
Proteínas do Envelope Viral/genética
[Mh] Termos MeSH secundário: Animais
Sequência de Bases
Linhagem Celular
Peste Suína Clássica/patologia
Vírus da Febre Suína Clássica/metabolismo
Cricetulus
Expressão Gênica
Engenharia Genética
Rim/virologia
Multimerização Proteica
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Suínos
Proteínas do Envelope Viral/metabolismo
Carga Viral
Virulência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Recombinant Proteins); 0 (Viral Envelope Proteins)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171229
[Lr] Data última revisão:
171229
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171214
[St] Status:MEDLINE
[do] DOI:10.1099/jgv.0.000990


  10 / 17860 MEDLINE  
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[PMID]:29216187
[Au] Autor:Stitz L; Vogel A; Schnee M; Voss D; Rauch S; Mutzke T; Ketterer T; Kramps T; Petsch B
[Ad] Endereço:Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
[Ti] Título:A thermostable messenger RNA based vaccine against rabies.
[So] Source:PLoS Negl Trop Dis;11(12):e0006108, 2017 Dec.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Although effective rabies virus vaccines have been existing for decades, each year, rabies virus infections still cause around 50.000 fatalities worldwide. Most of these cases occur in developing countries, where these vaccines are not available. The reasons for this are the prohibitive high costs of cell culture or egg grown rabies virus vaccines and the lack of a functional cold chain in many regions in which rabies virus is endemic. Here, we describe the excellent temperature resistance of a non-replicating mRNA based rabies virus vaccine encoding the rabies virus glycoprotein (RABV-G). Prolonged storage of the vaccine from -80°C to up to +70°C for several months did not impact the protective capacity of the mRNA vaccine. Efficacy after storage was demonstrated by the induction of rabies specific virus neutralizing antibodies and protection in mice against lethal rabies infection. Moreover, storing the vaccine at oscillating temperatures between +4° and +56°C for 20 cycles in order to simulate interruptions of the cold chain during vaccine transport, did not affect the vaccine's immunogenicity and protective characteristics, indicating that maintenance of a cold chain is not essential for this vaccine.
[Mh] Termos MeSH primário: Antígenos Virais/genética
Glicoproteínas/genética
Imunogenicidade da Vacina
RNA Mensageiro
Vacinas Antirrábicas/imunologia
Vírus da Raiva/genética
Raiva/prevenção & controle
Potência de Vacina
Proteínas do Envelope Viral/genética
[Mh] Termos MeSH secundário: Animais
Anticorpos Neutralizantes/sangue
Anticorpos Antivirais/sangue
Camundongos
Vacinas Antirrábicas/administração & dosagem
Vacinas Antirrábicas/genética
Vírus da Raiva/imunologia
Temperatura Ambiente
Vacinas Sintéticas/administração & dosagem
Vacinas Sintéticas/genética
Vacinas Sintéticas/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Neutralizing); 0 (Antibodies, Viral); 0 (Antigens, Viral); 0 (Glycoproteins); 0 (RNA, Messenger); 0 (Rabies Vaccines); 0 (Vaccines, Synthetic); 0 (Viral Envelope Proteins); 0 (glycoprotein G, Rabies virus)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171226
[Lr] Data última revisão:
171226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171208
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0006108



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