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  1 / 3709 MEDLINE  
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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


  2 / 3709 MEDLINE  
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Pissinatti, Alcides
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[PMID]:28931021
[Au] Autor:Muniz CP; Cavalcante LTF; Jia H; Zheng H; Tang S; Augusto AM; Pissinatti A; Fedullo LP; Santos AF; Soares MA; Switzer WM
[Ad] Endereço:Departamento de Genética, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
[Ti] Título:Zoonotic infection of Brazilian primate workers with New World simian foamy virus.
[So] Source:PLoS One;12(9):e0184502, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Simian foamy viruses (SFVs) are retroviruses present in nearly all nonhuman primates (NHPs), including Old World primates (OWP) and New World primates (NWP). While all confirmed human infections with SFV are from zoonotic transmissions originating from OWP, little is known about the zoonotic transmission potential of NWP SFV. We conducted a longitudinal, prospective study of 56 workers occupationally exposed to NWP in Brazil. Plasma from these workers was tested using Western blot (WB) assays containing NWP SFV antigens. Genomic DNA from blood and buccal swabs was analyzed for the presence of proviral SFV sequences by three nested PCR tests and a new quantitative PCR assay. Exposure histories were obtained and analyzed for associations with possible SFV infection. Ten persons (18%) tested seropositive and two persons were seroindeterminate (3.6%) for NWP SFV. Six persons had seroreactivity over 2-3 years suggestive of persistent infection. All SFV NWP WB-positive workers reported at least one incident involving NWP, including six reporting NWP bites. NWP SFV viral DNA was not detected in the blood or buccal swabs from all 12 NWP SFV seroreactive workers. We also found evidence of SFV seroreversion in three workers suggestive of possible clearance of infection. Our findings suggest that NWP SFV can be transmitted to occupationally-exposed humans and can elicit specific humoral immune responses but infection remains well-controlled resulting in latent infection and may occasionally clear.
[Mh] Termos MeSH primário: Infecções por Retroviridae/diagnóstico
Vírus Espumoso dos Símios/genética
Zoonoses/diagnóstico
[Mh] Termos MeSH secundário: Adulto
Animais
Antígenos Virais/imunologia
Antígenos Virais/metabolismo
Brasil
DNA Viral/sangue
DNA Viral/metabolismo
Feminino
Seres Humanos
Leucócitos Mononucleares/citologia
Leucócitos Mononucleares/virologia
Estudos Longitudinais
Masculino
Meia-Idade
Mucosa Bucal/virologia
Reação em Cadeia da Polimerase
Primatas
Estudos Prospectivos
Infecções por Retroviridae/transmissão
Infecções por Retroviridae/virologia
Risco
Vírus Espumoso dos Símios/isolamento & purificação
Zoonoses/virologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Viral); 0 (DNA, Viral)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171020
[Lr] Data última revisão:
171020
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170921
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184502


  3 / 3709 MEDLINE  
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[PMID]:28904191
[Au] Autor:Littwitz-Salomon E; Schimmer S; Dittmer U
[Ad] Endereço:Institute for Virology of the University Hospital Essen, University of Duisburg-Essen, Essen, Germany Elisabeth.Littwitz@uni-due.de.
[Ti] Título:Dose of Retroviral Infection Determines Induction of Antiviral NK Cell Responses.
[So] Source:J Virol;91(22), 2017 Nov 15.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Natural killer (NK) cells are part of the innate immune system and recognize virus-infected cells as well as tumor cells. Conflicting data about the beneficial or even detrimental role of NK cells in different infectious diseases have been described previously. While the type of pathogen strongly influences NK cell functionality, less is known about how the infection dose influences the quality of a NK cell response against retroviruses. In this study, we used the well-established Friend retrovirus (FV) mouse model to investigate the impact of virus dose on the induction of antiviral NK cell functions. High-dose virus inoculation increased initial virus replication compared to that with medium- or low-dose viral challenge and significantly improved NK cell activation. Antiviral NK cell activity, including cytotoxicity toward infected target cells, was also enhanced by high-dose virus infection. NK cell activation following high-dose viral challenge was likely mediated by activated dendritic cells (DCs) and macrophages and the NK cell-stimulating cytokines interleukin 15 (IL-15) and IL-18. Neutralization of these cytokines decreased NK cell functions and increased viral loads, whereas IL-15 and IL-18 therapy improved NK cell activity. Here we demonstrate that virus dose positively correlates with antiviral NK cell activity and function, which are at least partly driven by IL-15 and IL-18. Our results suggest that NK cell activity may be therapeutically enhanced by administering IL-15 and IL-18 in virus infections that inadequately activate NK cells. In infections with retroviruses, like HIV and FV infection of mice, NK cells clearly mediate antiviral activities, but they are usually not sufficient to prevent severe pathology. Here we show that the initial infection dose impacts the induction of an antiviral NK cell response during an acute retroviral infection, which had not investigated before. High-dose infection resulted in a strong NK cell functionality, whereas no antiviral activities were detected after low- or medium-dose infection. Interestingly, DCs and macrophages were highly activated after high-dose FV challenge, which corresponded with increased levels of NK cell-stimulating cytokines IL-15 and IL-18. IL-15 and IL-18 neutralization decreased NK cell functions, whereas IL-15 and IL-18 therapy improved NK cell activity. Here we show the importance of cytokines for NK cell activation in retroviral infections; our findings suggest that immunotherapy combining the well-tolerated cytokines IL-15 and IL-18 might be an interesting approach for antiretroviral treatment.
[Mh] Termos MeSH primário: Vírus da Leucemia Murina de Friend/imunologia
Células Matadoras Naturais/imunologia
Ativação Linfocitária
Infecções por Retroviridae/imunologia
[Mh] Termos MeSH secundário: Animais
Relação Dose-Resposta Imunológica
Feminino
Interleucina-15/imunologia
Interleucina-15/farmacologia
Interleucina-18/imunologia
Interleucina-18/farmacologia
Camundongos
Infecções por Retroviridae/tratamento farmacológico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Interleukin-15); 0 (Interleukin-18)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170915
[St] Status:MEDLINE


  4 / 3709 MEDLINE  
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[PMID]:28863180
[Au] Autor:Muniz CP; Zheng H; Jia H; Cavalcante LTF; Augusto AM; Fedullo LP; Pissinatti A; Soares MA; Switzer WM; Santos AF
[Ad] Endereço:Departamento de Genética, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
[Ti] Título:A non-invasive specimen collection method and a novel simian foamy virus (SFV) DNA quantification assay in New World primates reveal aspects of tissue tropism and improved SFV detection.
[So] Source:PLoS One;12(9):e0184251, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Simian foamy viruses (SFVs) co-evolved with a wide range of Old World and New World primates (OWPs and NWPs, respectively) and occasionally transmit to humans. Previous studies of OWPs showed that the predominant site of SFV replication is the oral mucosa. However, very little is known about SFV viral loads (VLs) in the oral mucosa or blood of NWPs. NWPs have smaller body sizes, limiting collection of sufficient whole blood volumes to molecularly detect and quantify SFV. Our study evaluated the use of noninvasively collected buccal swabs to detect NWP SFV compared with detection in blood using a new NWP SFV quantitative PCR (qPCR) assay. Buccal and blood samples were collected from 107 captive NWPs in Brazil comprising eleven distinct genera at the Primate Center of Rio de Janeiro (n = 58) and at Fundação Jardim Zoológico da Cidade do Rio Janeiro (n = 49). NWP SFV western blot (WB) testing was performed on a subset of animals for comparison with PCR results. The qPCR assay was validated using distinct SFV polymerase sequences from seven NWP genera (Callithrix, Sapajus, Saimiri, Ateles, Alouatta, Cacajao and Pithecia). Assay sensitivity was 20 copies/106 cells, detectable in 90% of replicates. SFV DNA VLs were higher in buccal swabs (5 log copies/106 cells) compared to peripheral blood mononuclear cells (PBMCs) (3 log copies/106 cells). The qPCR assay was also more sensitive than nested PCR for detection of NWP SFV infection and identified an additional 27 SFV-infected monkeys of which 18 (90%) were WB-positive and three that were WB-negative. We show the utility of using both blood and buccal swabs and our new qPCR assay for detection and quantification of diverse NWP SFV, which will assist a better understanding of the epidemiology of SFV in NWPs and any potential zoonotic infection risk for humans exposed to NWPs.
[Mh] Termos MeSH primário: Leucócitos Mononucleares/virologia
Primatas/virologia
Infecções por Retroviridae/diagnóstico
Vírus Espumoso dos Símios/genética
Manejo de Espécimes/métodos
[Mh] Termos MeSH secundário: Animais
Brasil
DNA Viral/genética
Seres Humanos
Doenças dos Macacos/diagnóstico
Doenças dos Macacos/virologia
Mucosa Bucal/virologia
Filogenia
Plasmídeos/metabolismo
Reação em Cadeia da Polimerase
Reação em Cadeia da Polimerase em Tempo Real
Infecções por Retroviridae/veterinária
Sensibilidade e Especificidade
Especificidade da Espécie
Tropismo Viral
Zoonoses/virologia
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Viral)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170902
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184251


  5 / 3709 MEDLINE  
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[PMID]:28813660
[Au] Autor:Denzin LK; Khan AA; Virdis F; Wilks J; Kane M; Beilinson HA; Dikiy S; Case LK; Roopenian D; Witkowski M; Chervonsky AV; Golovkina TV
[Ad] Endereço:Child Health Institute of NJ, Department of Pediatrics, Rutgers Robert Wood Johnson Medical School, Rutgers, The State University of NJ, New Brunswick, NJ 08901, USA.
[Ti] Título:Neutralizing Antibody Responses to Viral Infections Are Linked to the Non-classical MHC Class II Gene H2-Ob.
[So] Source:Immunity;47(2):310-322.e7, 2017 Aug 15.
[Is] ISSN:1097-4180
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Select humans and animals control persistent viral infections via adaptive immune responses that include production of neutralizing antibodies. The precise genetic basis for the control remains enigmatic. Here, we report positional cloning of the gene responsible for production of retrovirus-neutralizing antibodies in mice of the I/LnJ strain. It encodes the beta subunit of the non-classical major histocompatibility complex class II (MHC-II)-like molecule H2-O, a negative regulator of antigen presentation. The recessive and functionally null I/LnJ H2-Ob allele supported the production of virus-neutralizing antibodies independently of the classical MHC haplotype. Subsequent bioinformatics and functional analyses of the human H2-Ob homolog, HLA-DOB, revealed both loss- and gain-of-function alleles, which could affect the ability of their carriers to control infections with human hepatitis B (HBV) and C (HCV) viruses. Thus, understanding of the previously unappreciated role of H2-O (HLA-DO) in immunity to infections may suggest new approaches in achieving neutralizing immunity to viruses.
[Mh] Termos MeSH primário: Anticorpos Neutralizantes
Antígenos HLA-D/metabolismo
Antígenos de Histocompatibilidade Classe II/metabolismo
Imunidade Humoral
Vírus do Tumor Mamário do Camundongo/imunologia
Vírus Rauscher/imunologia
Infecções por Retroviridae/imunologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Neutralizantes/metabolismo
Anticorpos Antivirais/metabolismo
Apresentação do Antígeno/genética
Biologia Computacional
Feminino
Predisposição Genética para Doença
Antígenos HLA-D/genética
Células HeLa
Hepatite B/imunologia
Hepatite B/transmissão
Hepatite C/imunologia
Hepatite C/transmissão
Antígenos de Histocompatibilidade Classe II/genética
Seres Humanos
Imunidade Humoral/genética
Masculino
Camundongos
Camundongos Endogâmicos
Camundongos Knockout
Mutação/genética
Polimorfismo Genético
Infecções por Retroviridae/transmissão
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Neutralizing); 0 (Antibodies, Viral); 0 (H-2O antigen); 0 (HLA-D Antigens); 0 (HLA-DO antigens); 0 (Histocompatibility Antigens Class II)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170928
[Lr] Data última revisão:
170928
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170817
[St] Status:MEDLINE


  6 / 3709 MEDLINE  
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[PMID]:28809145
[Au] Autor:Konstantoulas CJ; Hagen B; Indik S
[Ad] Endereço:Institute of Virology, University of Veterinary Medicine, Veterinaerplatz 1, 1210 Vienna, Austria.
[Ti] Título:Moderate sensitivity of mouse mammary tumour virus to inhibition by human APOBEC3G.
[So] Source:J Gen Virol;98(9):2362-2367, 2017 Sep.
[Is] ISSN:1465-2099
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Infectivity of the mouse mammary tumour virus (MMTV) is inhibited by mouse APOBEC3 (mA3) which is efficiently packaged into virions. As the inhibition is only partial, the virus can replicate in tissues expressing mA3 and complete its replication cycle. Here, we have examined the sensitivity of MMTV to inhibition by a human orthologue of mA3, A3G. We report that the virus containing A3G is only moderately susceptible to inhibition by the human factor. Whereas the vif-deficient HIV-1 vector produced in human epithelial cells expressing endogenous levels of A3G was efficiently inhibited, an MMTV vector remained fully infectious. Greater A3G expression levels were necessary to restrict infectivity of MMTV, but only when the factor retained its deaminase activity. Furthermore, the spreading kinetic of a replication competent MMTV was only moderately accelerated in cells with downmodulated A3G expression. These data suggest that MMTV has evolved a mechanism to neutralize antiviral activity of APOBEC3 proteins.
[Mh] Termos MeSH primário: Desaminase APOBEC-3G/metabolismo
Vírus do Tumor Mamário do Camundongo/fisiologia
Infecções por Retroviridae/veterinária
Doenças dos Roedores/enzimologia
[Mh] Termos MeSH secundário: Desaminase APOBEC-3G/genética
Animais
Seres Humanos
Vírus do Tumor Mamário do Camundongo/genética
Camundongos
Infecções por Retroviridae/enzimologia
Infecções por Retroviridae/genética
Infecções por Retroviridae/virologia
Doenças dos Roedores/genética
Doenças dos Roedores/virologia
Montagem de Vírus
Replicação Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 3.5.4.5 (APOBEC-3G Deaminase); EC 3.5.4.5 (APOBEC3G protein, human); EC 3.5.4.5 (APOBEC3G protein, mouse)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170919
[Lr] Data última revisão:
170919
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170816
[St] Status:MEDLINE
[do] DOI:10.1099/jgv.0.000897


  7 / 3709 MEDLINE  
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[PMID]:28794032
[Au] Autor:Bamunusinghe D; Liu Q; Plishka R; Dolan MA; Skorski M; Oler AJ; Yedavalli VRK; Buckler-White A; Hartley JW; Kozak CA
[Ad] Endereço:Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
[Ti] Título:Recombinant Origins of Pathogenic and Nonpathogenic Mouse Gammaretroviruses with Polytropic Host Range.
[So] Source:J Virol;91(21), 2017 Nov 01.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ecotropic, xenotropic, and polytropic mouse leukemia viruses (E-, X-, and P-MLVs) exist in mice as infectious viruses and endogenous retroviruses (ERVs) inserted into mouse chromosomes. All three MLV subgroups are linked to leukemogenesis, which involves generation of recombinants with polytropic host range. Although P-MLVs are deemed to be the proximal agents of disease induction, few biologically characterized infectious P-MLVs have been sequenced for comparative analysis. We analyzed the complete genomes of 16 naturally occurring infectious P-MLVs, 12 of which were typed for pathogenic potential. We sought to identify ERV progenitors, recombinational hot spots, and segments that are always replaced, never replaced, or linked to pathogenesis or host range. Each P-MLV has an E-MLV backbone with P- or X-ERV replacements that together cover 100% of the recombinant genomes, with different substitution patterns for X- and P-ERVs. Two segments are always replaced, both coding for envelope (Env) protein segments: the N terminus of the surface subunit and the cytoplasmic tail R peptide. Viral gene replacements are influenced by host restriction genes and Pathogenic potential maps to the transmembrane subunit segment encoding the N-heptad repeat (HR1). Molecular dynamics simulations identified three novel interdomain salt bridges in the lymphomagenic virus HR1 that could affect structural stability, entry or sensitivity to host immune responses. The long terminal repeats of lymphomagenic P-MLVs are differentially altered by recombinations, duplications, or mutations. This analysis of the naturally occurring, sometimes pathogenic P-MLV recombinants defines the limits and extent of intersubgroup recombination and identifies specific sequence changes linked to pathogenesis and host interactions. During virus-induced leukemogenesis, ecotropic mouse leukemia viruses (MLVs) recombine with nonecotropic endogenous retroviruses (ERVs) to produce polytropic MLVs (P-MLVs). Analysis of 16 P-MLV genomes identified two segments consistently replaced: one at the envelope N terminus that alters receptor choice and one in the R peptide at the envelope C terminus, which is removed during virus assembly. Genome-wide analysis shows that nonecotropic replacements in the progenitor ecotropic MLV genome are more extensive than previously appreciated, covering 100% of the genome; contributions from xenotropic and polytropic ERVs differentially alter the regions responsible for receptor determination or subject to APOBEC3 and Fv1 restriction. All pathogenic viruses had modifications in the regulatory elements in their long terminal repeats and differed in a helical segment of envelope involved in entry and targeted by the host immune system. Virus-induced leukemogenesis thus involves generation of complex recombinants, and specific replacements are linked to pathogenesis and host restrictions.
[Mh] Termos MeSH primário: Especificidade de Hospedeiro/genética
Vírus da Leucemia Murina/classificação
Vírus da Leucemia Murina/patogenicidade
Leucemia Experimental/virologia
Infecções por Retroviridae/virologia
Infecções Tumorais por Vírus/virologia
Proteínas Virais/genética
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Sequência de Bases
Evolução Molecular
Genoma Viral
Vírus da Leucemia Murina/genética
Camundongos
Simulação de Dinâmica Molecular
Conformação Proteica
Receptores Virais/genética
Receptores Virais/metabolismo
Homologia de Sequência
Sequências Repetidas Terminais
Proteínas Virais/química
Proteínas Virais/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, Virus); 0 (Viral Proteins)
[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:170811
[St] Status:MEDLINE


  8 / 3709 MEDLINE  
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[PMID]:28437635
[Au] Autor:Colon-Moran W; Argaw T; Wilson CA
[Ad] Endereço:Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
[Ti] Título:Three cysteine residues of SLC52A1, a receptor for the porcine endogenous retrovirus-A (PERV-A), play a critical role in cell surface expression and infectivity.
[So] Source:Virology;507:140-150, 2017 Jul.
[Is] ISSN:1096-0341
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Porcine endogenous retrovirus-A (PERV-A), a gammaretrovirus, infects human cells in vitro, thus raising the potential risk of cross-species transmission in xenotransplantation. Two members of the solute carrier family 52 (SLC52A1 and SLC52A2) are PERV-A receptors. Site-directed mutagenesis of the cDNA encoding SLC52A1 identified that only one of two putative glycosylation signals is occupied by glycans. In addition, we showed that glycosylation of SLC52A1 is not necessary for PERV-A receptor function. We also identified that at a minimum, three cysteine residues are sufficient for SLC52A1 cell surface expression. Mutation of cysteine at position 365 and either of the two cysteine residues in the C-terminal tail at positions 442 or 446 reduced SLC52A1 surface expression and PERV-A infection suggesting that these residues may contribute to overall structural stability and receptor function. Understanding interactions between PERV-A and its cellular receptor may provide novel strategies to prevent zoonotic infection in the setting of xenotransplantation.
[Mh] Termos MeSH primário: Cisteína/metabolismo
Retrovirus Endógenos/patogenicidade
Gammaretrovirus/metabolismo
Receptores Acoplados a Proteínas-G/química
Receptores Virais/química
Receptores Virais/metabolismo
Infecções por Retroviridae/veterinária
Doenças dos Suínos/metabolismo
[Mh] Termos MeSH secundário: Animais
Cisteína/química
Cisteína/genética
Retrovirus Endógenos/genética
Retrovirus Endógenos/fisiologia
Gammaretrovirus/classificação
Gammaretrovirus/genética
Glicosilação
Receptores Acoplados a Proteínas-G/genética
Receptores Acoplados a Proteínas-G/metabolismo
Receptores Virais/genética
Infecções por Retroviridae/genética
Infecções por Retroviridae/metabolismo
Infecções por Retroviridae/virologia
Suínos
Doenças dos Suínos/genética
Doenças dos Suínos/virologia
Virulência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, G-Protein-Coupled); 0 (Receptors, Virus); K848JZ4886 (Cysteine)
[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:170425
[St] Status:MEDLINE


  9 / 3709 MEDLINE  
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[PMID]:28381565
[Au] Autor:Liberatore RA; Mastrocola EJ; Powell C; Bieniasz PD
[Ad] Endereço:Aaron Diamond AIDS Research Center, New York, New York, USA.
[Ti] Título:Tetherin Inhibits Cell-Free Virus Dissemination and Retards Murine Leukemia Virus Pathogenesis.
[So] Source:J Virol;91(12), 2017 Jun 15.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The relative contributions of cell-free virion circulation and direct cell-to-cell transmission to retroviral dissemination and pathogenesis are unknown. Tetherin/Bst2 is an antiviral protein that blocks enveloped virion release into the extracellular milieu but may not inhibit cell-to-cell virus transmission. We developed live-cell imaging assays which show that tetherin does not affect Moloney murine leukemia virus (MoMLV) spread, and only minimally affects vesicular stomatitis virus (VSV) spread, to adjacent cells in a monolayer. Conversely, cell-free MLV and VSV virion yields and VSV spread to distal cells were dramatically reduced by tetherin. To elucidate the roles of tetherin and cell-free virions during viral dissemination and pathogenesis, we developed mice carrying an inducible human tetherin (hTetherin) transgene. While ubiquitous hTetherin expression was detrimental to the growth and survival of mice, restriction of hTetherin expression to hematopoietic cells gave apparently healthy mice. The expression of hTetherin in hematopoietic cells had little or no effect on the number of MoMLV-infected splenocytes and thymocytes. However, hTetherin expression significantly reduced cell-free plasma viremia and also delayed MoMLV-induced disease. Overall, these results suggest that MoMLV spread within hematopoietic tissues and cell monolayers involves cell-to-cell transmission that is resistant to tetherin but that virion dissemination via plasma is inhibited by tetherin and is required for full MoMLV pathogenesis. Retroviruses are thought to spread primarily via direct cell-to-cell transmission, yet many have evolved to counteract an antiviral protein called tetherin, which may selectively inhibit cell-free virus release. We generated a mouse model with an inducible tetherin transgene in order to study how tetherin affects retroviral dissemination and on which cell types its expression is required to do so. We first developed a novel live-cell imaging assay to demonstrate that while tetherin does indeed dramatically reduce cell-free virus spreading, it has little to no effect on direct cell-to-cell transmission of either vesicular stomatitis virus (VSV) or the retrovirus MoMLV. Using our transgenic mouse model, we found that tetherin expression on hematopoietic cells resulted in the specific reduction of MoMLV cell-free plasma viremia but not the number of infected hematopoietic cells. The delay in disease associated with this scenario suggests a role for cell-free virus in retroviral disease progression.
[Mh] Termos MeSH primário: Antígenos CD/metabolismo
Vírus da Leucemia Murina de Moloney/fisiologia
Infecções por Retroviridae/virologia
Vírus da Estomatite Vesicular Indiana/fisiologia
Internalização do Vírus
Liberação de Vírus
[Mh] Termos MeSH secundário: Animais
Antígenos CD/genética
Antígenos CD/farmacologia
Proteínas Ligadas por GPI/genética
Proteínas Ligadas por GPI/metabolismo
Proteínas Ligadas por GPI/farmacologia
Células-Tronco Hematopoéticas/metabolismo
Células-Tronco Hematopoéticas/virologia
Seres Humanos
Camundongos
Camundongos Transgênicos
Células NIH 3T3
Baço/citologia
Baço/virologia
Timócitos/virologia
Viremia
Vírion/metabolismo
Replicação Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD); 0 (BST2 protein, human); 0 (GPI-Linked Proteins)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170727
[Lr] Data última revisão:
170727
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170407
[St] Status:MEDLINE


  10 / 3709 MEDLINE  
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[PMID]:28314126
[Au] Autor:Spannaus R; Miller C; Lindemann D; Bodem J
[Ad] Endereço:Institut für Virologie und Immunbiologie, Julius-Maximilians-Universität Würzburg, Germany.
[Ti] Título:Purification of foamy viral particles.
[So] Source:Virology;506:28-33, 2017 Jun.
[Is] ISSN:1096-0341
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Foamy viruses are non-pathogenic retroviruses and represent a tool for vector development. For gene therapy applications and for analyses of viral protein composition infectious particles need to be purified, which has been difficult for foamy viruses in the past. Here, we describe a novel, simple, and fast purification method for prototype foamy viruses with high purity using size exclusion and affinity chromatography. More than 99,9% of the contaminating proteins were removed. The purified viruses were used to determine the amount of the incorporated Pol protein relative to Gag. The determined Gag to Pol PR-RT ratio of 30:1 confirmed previous studies suggesting FV virions encapsidate fewer number of Pol molecules than orthoretroviruses.
[Mh] Termos MeSH primário: Cromatografia de Afinidade/métodos
Cromatografia em Gel/métodos
Spumavirus/crescimento & desenvolvimento
Vírion/crescimento & desenvolvimento
[Mh] Termos MeSH secundário: Regulação Viral da Expressão Gênica
Produtos do Gene pol/genética
Produtos do Gene pol/metabolismo
Seres Humanos
Infecções por Retroviridae/virologia
Spumavirus/genética
Spumavirus/isolamento & purificação
Spumavirus/fisiologia
Vírion/genética
Vírion/isolamento & purificação
Vírion/fisiologia
Montagem de Vírus
Cultura de Vírus
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Gene Products, pol)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170705
[Lr] Data última revisão:
170705
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170318
[St] Status:MEDLINE



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