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[PMID]:28972091
[Au] Autor:Patel SJ; Yokoyama WM
[Ad] Endereço:Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110; and.
[Ti] Título:CD8 T Cells Prevent Lethality from Neonatal Murine Roseolovirus Infection.
[So] Source:J Immunol;199(9):3212-3221, 2017 Nov 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A recently described mouse homolog of the human roseoloviruses, murine roseolovirus (MRV), causes loss of peripheral and thymic CD4 cells during neonatal infection of BALB/c mice. Despite significant disruptions to the normal adaptive immune response, infected BALB/c mice reproducibly recover from infection, consistent with prior studies on a related virus, mouse thymic virus. In this article, we show that, in contrast to published studies on mouse thymic virus, MRV appears to robustly infect neonatal C57BL/6 (B6) mice, causing severe depletion of thymocytes and peripheral T cells. Moreover, B6 mice recovered from infection. We investigated the mechanism of thymocyte and T cell loss, determining that the major thymocyte subsets were infected with MRV; however, CD4 and CD4 CD8 T cells showed increased apoptosis during infection. We found that CD8 T cells populated MRV-infected thymi. These CD8 T cells expressed markers of activation, had restricted TCR repertoire, and accumulated intracellular effector proteins, consistent with a cytotoxic lymphocyte phenotype and suggesting their involvement in viral clearance. Indeed, absence of CD8 T cells prevented recovery from MRV infection and led to lethality in infected animals, whereas B cell-deficient mice showed CD4 T cell loss but recovered from infection without lethality. Thus, these results demonstrate that CD8 T cells are required for protective immunity against a naturally occurring murine pathogen that infects the thymus and establish a novel infection model for MRV in B6 mice, providing the foundation for detailed future studies on MRV with the availability of innumerable mutant mice on the B6 background.
[Mh] Termos MeSH primário: Linfócitos T CD8-Positivos/imunologia
Infecções por Roseolovirus/imunologia
Roseolovirus/imunologia
Timo/imunologia
[Mh] Termos MeSH secundário: Animais
Linfócitos T CD4-Positivos/imunologia
Linfócitos T CD4-Positivos/patologia
Linfócitos T CD8-Positivos/patologia
Camundongos
Camundongos Knockout
Infecções por Roseolovirus/genética
Infecções por Roseolovirus/patologia
Timo/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171004
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1700982


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[PMID]:28651121
[Au] Autor:Coleman S; Choi KY; McGregor A
[Ad] Endereço:Department of Microbial Pathogenesis & Immunology, Texas A&M University, Health Science Center, College of Medicine, College Station, TX, United States.
[Ti] Título:Cytomegalovirus UL128 homolog mutants that form a pentameric complex produce virus with impaired epithelial and trophoblast cell tropism and altered pathogenicity in the guinea pig.
[So] Source:Virology;509:205-221, 2017 Sep.
[Is] ISSN:1096-0341
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Guinea pig cytomegalovirus (GPCMV) encodes a homolog pentameric complex (PC) for specific cell tropism and congenital infection. In human cytomegalovirus, the PC is an important antibody neutralizing target and GPCMV studies will aid in the development of intervention strategies. Deletion mutants of the C-terminal domains of unique PC proteins (UL128, UL130 and UL131 homologs) were unable to form a PC in separate transient expression assays. Minor modifications to the UL128 homolog (GP129) C-terminal domain enabled PC formation but viruses encoding these mutants had altered tropism to renal and placental trophoblast cells. Mutation of the presumptive CC chemokine motif encoded by GP129 was investigated by alanine substitution of the CC motif (codons 26-27) and cysteines (codons 47 and 62). GP129 chemokine mutants formed PC but GP129 chemokine mutant viruses had reduced epitropism. A GP129 chemokine mutant virus pathogenicity study demonstrated reduced viral load to target organs but highly extended viremia.
[Mh] Termos MeSH primário: Células Epiteliais/virologia
Proteínas Mutantes/metabolismo
Multimerização Proteica
Roseolovirus/fisiologia
Trofoblastos/virologia
Proteínas do Envelope Viral/metabolismo
Tropismo Viral
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Animais
Análise Mutacional de DNA
Cobaias
Mutagênese Sítio-Dirigida
Proteínas Mutantes/genética
Roseolovirus/genética
Infecções por Roseolovirus/patologia
Infecções por Roseolovirus/veterinária
Infecções por Roseolovirus/virologia
Proteínas do Envelope Viral/genética
Viremia/patologia
Viremia/veterinária
Viremia/virologia
Virulência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Mutant Proteins); 0 (Viral Envelope Proteins)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170721
[Lr] Data última revisão:
170721
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170627
[St] Status:MEDLINE


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[PMID]:28314105
[Au] Autor:Sang Y; Zhang R; Creagh AL; Haynes CA; Straus SK
[Ad] Endereço:a Department of Chemistry, The University of British Columbia, Vancouver, BC V6T 1Z1, Canada.
[Ti] Título:Interactions of U24 from Roseolovirus with WW domains: canonical vs noncanonical.
[So] Source:Biochem Cell Biol;95(3):350-358, 2017 Jun.
[Is] ISSN:1208-6002
[Cp] País de publicação:Canada
[La] Idioma:eng
[Ab] Resumo:U24 is a C-terminal membrane-anchored protein found in both human herpes virus type 6 and 7 (HHV-6 and HHV-7), with an N-terminal segment that is rich in prolines (PPxY motif in both HHV-6A and 7; PxxP motif in HHV-6A). Previous work has shown that U24 interacts strongly with Nedd4 WW domains, in particular, hNedd4L-WW3*. It was also shown that this interaction depends strongly on the nature of the amino acids that are upstream from the PY motif in U24. In this contribution, data was obtained from pull-downs, isothermal titration calorimetry, and NMR to further determine what modulates U24:WW domain interactions. Specifically, 3 non-canonical WW domains from human Smad ubiquitination regulatory factor (Smurf), namely hSmurf2-WW2, hSmurf2-WW3, and a tandem construct hSmurf2-WW2 + 3, were studied. Overall, the interactions between U24 and these Smurf WW domains were found to be weaker than those in U24:Nedd4 WW domain pairs, suggesting that U24 function is tightly linked to specific E3 ubiqitin ligases.
[Mh] Termos MeSH primário: Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo
Roseolovirus/metabolismo
Ubiquitina-Proteína Ligases/metabolismo
Proteínas Virais/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Complexos Endossomais de Distribuição Requeridos para Transporte/química
Complexos Endossomais de Distribuição Requeridos para Transporte/genética
Seres Humanos
Ubiquitina-Proteína Ligases Nedd4
Ligação Proteica
Conformação Proteica
Domínios Proteicos
Homologia de Sequência de Aminoácidos
Ubiquitina-Proteína Ligases/química
Ubiquitina-Proteína Ligases/genética
Proteínas Virais/química
Proteínas Virais/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Endosomal Sorting Complexes Required for Transport); 0 (Viral Proteins); EC 2.3.2.26 (Nedd4 Ubiquitin Protein Ligases); EC 2.3.2.26 (Nedd4 protein, human); EC 2.3.2.26 (SMURF2 protein, human); EC 2.3.2.27 (Ubiquitin-Protein Ligases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170318
[St] Status:MEDLINE
[do] DOI:10.1139/bcb-2016-0250


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[PMID]:28189970
[Au] Autor:Hornig J; Choi KY; McGregor A
[Ad] Endereço:Department of Microbial Pathogenesis & Immunology, Texas A&M University, Health Science Center, College of Medicine, College Station, TX, United States.
[Ti] Título:The essential role of guinea pig cytomegalovirus (GPCMV) IE1 and IE2 homologs in viral replication and IE1-mediated ND10 targeting.
[So] Source:Virology;504:122-140, 2017 Apr.
[Is] ISSN:1096-0341
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Guinea pig cytomegalovirus (GPCMV) immediate early proteins, IE1 and IE2, demonstrated structural and functional homologies with human cytomegalovirus (HCMV). GPCMV IE1 and IE2 co-localized in the nucleus with each other, the viral polymerase and guinea pig ND10 components (gpPML, gpDaxx, gpSp100, gpATRX). IE1 showed direct interaction with ND10 components by immunoprecipitation unlike IE2. Additionally, IE1 protein disrupted ND10 bodies. IE1 mutagenesis mapped the nuclear localization signal to the C-terminus and identified the core domain for gpPML interaction. Individual knockout of GPCMV GP122 or GP123 (IE2 and IE1 unique exons respectively) was lethal to the virus. However, an IE1 mutant (codons 234-474 deleted), was viable with attenuated viral growth kinetics and increased susceptibility to type I interferon (IFN-I). In HCMV, the IE proteins are important T cell target antigens. Consequently, characterization of the homologs in GPCMV provides a basis for their evaluation in candidate vaccines against congenital infection.
[Mh] Termos MeSH primário: Citomegalovirus/genética
Proteínas Imediatamente Precoces/genética
Proteínas Nucleares/metabolismo
Roseolovirus/genética
Transativadores/genética
Replicação Viral/genética
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Núcleo Celular/virologia
Clonagem Molecular
Citomegalovirus/imunologia
Técnicas de Inativação de Genes
Cobaias
Seres Humanos
Proteínas Imediatamente Precoces/imunologia
Proteínas Imediatamente Precoces/metabolismo
Interferon Tipo I/farmacologia
Janus Quinases/metabolismo
Janus Quinases/farmacologia
Proteínas Nucleares/genética
Pirazóis/farmacologia
Roseolovirus/efeitos dos fármacos
Roseolovirus/imunologia
Transdução de Sinais/genética
Transativadores/imunologia
Transativadores/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (IE1 protein, cytomegalovirus); 0 (IE2 protein, Cytomegalovirus); 0 (INCB018424); 0 (Immediate-Early Proteins); 0 (Interferon Type I); 0 (Nuclear Proteins); 0 (Pyrazoles); 0 (Trans-Activators); 0 (nuclear dot protein 52, human); EC 2.7.10.2 (Janus Kinases)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170714
[Lr] Data última revisão:
170714
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170213
[St] Status:MEDLINE


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[PMID]:28036408
[Au] Autor:Pozo F; Juste J; Vázquez-Morón S; Aznar-López C; Ibáñez C; Garin I; Aihartza J; Casas I; Tenorio A; Echevarría JE
[Ad] Endereço:Virology Section, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
[Ti] Título:Identification of Novel Betaherpesviruses in Iberian Bats Reveals Parallel Evolution.
[So] Source:PLoS One;11(12):e0169153, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A thorough search for bat herpesviruses was carried out in oropharyngeal samples taken from most of the bat species present in the Iberian Peninsula from the Vespertilionidae, Miniopteridae, Molossidae and Rhinolophidae families, in addition to a colony of captive fruit bats from the Pteropodidae family. By using two degenerate consensus PCR methods targeting two conserved genes, distinct and previously unrecognized bat-hosted herpesviruses were identified for the most of the tested species. All together a total of 42 potentially novel bat herpesviruses were partially characterized. Thirty-two of them were tentatively assigned to the Betaherpesvirinae subfamily while the remaining 10 were allocated into the Gammaherpesvirinae subfamily. Significant diversity was observed among the novel sequences when compared with type herpesvirus species of the ICTV-approved genera. The inferred phylogenetic relationships showed that most of the betaherpesviruses sequences fell into a well-supported unique monophyletic clade and support the recognition of a new betaherpesvirus genus. This clade is subdivided into three major clades, corresponding to the families of bats studied. This supports the hypothesis of a species-specific parallel evolution process between the potentially new betaherpesviruses and their bat hosts. Interestingly, two of the betaherpesviruses' sequences detected in rhinolophid bats clustered together apart from the rest, closely related to viruses that belong to the Roseolovirus genus. This suggests a putative third roseolo lineage. On the contrary, no phylogenetic structure was detected among several potentially novel bat-hosted gammaherpesviruses found in the study. Remarkably, all of the possible novel bat herpesviruses described in this study are linked to a unique bat species.
[Mh] Termos MeSH primário: Betaherpesvirinae/crescimento & desenvolvimento
Betaherpesvirinae/genética
Quirópteros/virologia
DNA Viral/genética
Gammaherpesvirinae/classificação
Gammaherpesvirinae/genética
[Mh] Termos MeSH secundário: Animais
Sequência de Bases
Betaherpesvirinae/classificação
Betaherpesvirinae/isolamento & purificação
Evolução Biológica
Gammaherpesvirinae/isolamento & purificação
Variação Genética/genética
Filogenia
Reação em Cadeia da Polimerase
Portugal
Roseolovirus/classificação
Roseolovirus/genética
Alinhamento de Sequência
Análise de Sequência de DNA
Espanha
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Viral)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170713
[Lr] Data última revisão:
170713
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161231
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0169153


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[PMID]:27334585
[Au] Autor:Choi KY; Root M; McGregor A
[Ad] Endereço:Department of Microbial Pathogenesis and Immunology, Texas A&M University, Health Science Center, College of Medicine, College Station, Texas, USA.
[Ti] Título:A Novel Non-Replication-Competent Cytomegalovirus Capsid Mutant Vaccine Strategy Is Effective in Reducing Congenital Infection.
[So] Source:J Virol;90(17):7902-19, 2016 Sep 01.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:UNLABELLED: Congenital cytomegalovirus (CMV) infection is a leading cause of mental retardation and deafness in newborns. The guinea pig is the only small animal model for congenital CMV infection. A novel CMV vaccine was investigated as an intervention strategy against congenital guinea pig cytomegalovirus (GPCMV) infection. In this disabled infectious single-cycle (DISC) vaccine strategy, a GPCMV mutant virus was used that lacked the ability to express an essential capsid gene (the UL85 homolog GP85) except when grown on a complementing cell line. In vaccinated animals, the GP85 mutant virus (GP85 DISC) induced an antibody response to important glycoprotein complexes considered neutralizing target antigens (gB, gH/gL/gO, and gM/gN). The vaccine also generated a T cell response to the pp65 homolog (GP83), determined via a newly established guinea pig gamma interferon enzyme-linked immunosorbent spot assay. In a congenital infection protection study, GP85 DISC-vaccinated animals and a nonvaccinated control group were challenged during pregnancy with wild-type GPCMV (10(5) PFU). The pregnant animals carried the pups to term, and viral loads in target organs of pups were analyzed. Based on live pup births in the vaccinated and control groups (94.1% versus 63.6%), the vaccine was successful in reducing mortality (P = 0.0002). Additionally, pups from the vaccinated group had reduced CMV transmission, with 23.5% infected target organs versus 75.9% in the control group. Overall, these preliminary studies indicate that a DISC CMV vaccine strategy has the ability to induce an immune response similar to that of natural virus infection but has the increased safety of a non-replication-competent virus, which makes this approach attractive as a CMV vaccine strategy. IMPORTANCE: Congenital CMV infection is a leading cause of mental retardation and deafness in newborns. An effective vaccine against CMV remains an elusive goal despite over 50 years of CMV research. The guinea pig, with a placenta structure similar to that in humans, is the only small animal model for congenital CMV infection and recapitulates disease symptoms (e.g., deafness) in newborn pups. In this report, a novel vaccine strategy against congenital guinea pig cytomegalovirus (GPCMV) infection was developed, characterized, and tested for efficacy. This disabled infectious single-cycle (DISC) vaccine strategy induced a neutralizing antibody or a T cell response to important target antigens. In a congenital infection protection study, animals were protected against CMV in comparison to the nonvaccinated group (52% reduction of transmission). This novel vaccine was more effective than previously tested gB-based vaccines and most other strategies involving live virus vaccines. Overall, the DISC vaccine is a safe and promising approach against congenital CMV infection.
[Mh] Termos MeSH primário: Proteínas do Capsídeo/genética
Vacinas contra Citomegalovirus/imunologia
Proteínas Mutantes/genética
Infecções por Roseolovirus/congênito
Infecções por Roseolovirus/prevenção & controle
Roseolovirus/fisiologia
Replicação Viral
[Mh] Termos MeSH secundário: Estruturas Animais/virologia
Animais
Anticorpos Neutralizantes/sangue
Anticorpos Antivirais/sangue
Vacinas contra Citomegalovirus/administração & dosagem
Vacinas contra Citomegalovirus/genética
ELISPOT
Interferon gama/secreção
Roseolovirus/genética
Análise de Sobrevida
Linfócitos T/imunologia
Resultado do Tratamento
Vacinas Sintéticas/administração & dosagem
Vacinas Sintéticas/genética
Vacinas Sintéticas/imunologia
Carga Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Neutralizing); 0 (Antibodies, Viral); 0 (Capsid Proteins); 0 (Cytomegalovirus Vaccines); 0 (Mutant Proteins); 0 (Vaccines, Synthetic); 82115-62-6 (Interferon-gamma)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170509
[Lr] Data última revisão:
170509
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160624
[St] Status:MEDLINE
[do] DOI:10.1128/JVI.00283-16


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[PMID]:27307567
[Au] Autor:McVoy MA; Wang JB; Dittmer DP; Bierle CJ; Swanson EC; Fernández-Alarcón C; Hernandez-Alvarado N; Zabeli JC; Schleiss MR
[Ad] Endereço:Department of Pediatrics, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA.
[Ti] Título:Repair of a Mutation Disrupting the Guinea Pig Cytomegalovirus Pentameric Complex Acquired during Fibroblast Passage Restores Pathogenesis in Immune-Suppressed Guinea Pigs and in the Context of Congenital Infection.
[So] Source:J Virol;90(17):7715-27, 2016 Sep 01.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:UNLABELLED: Guinea pig cytomegalovirus (GPCMV) provides a valuable model for congenital cytomegalovirus transmission. Salivary gland (SG)-passaged stocks of GPCMV are pathogenic, while tissue culture (TC) passage in fibroblasts results in attenuation. Nonpathogenic TC-derived virus N13R10 (cloned as a bacterial artificial chromosome [BAC]) has a 4-bp deletion that disrupts GP129, which encodes a subunit of the GPCMV pentameric complex (PC) believed to govern viral entry into select cell types, and GP130, an overlapping open reading frame (ORF) of unknown function. To determine if this deletion contributes to attenuation of N13R10, markerless gene transfer in Escherichia coli was used to construct virus r129, a variant of N13R10 in which the 4-bp deletion is repaired. Virions from r129 were found to contain GP129 as well as two other PC subunit proteins, GP131 and GP133, whereas these three PC subunits were absent from N13R10 virions. Replication of r129 in fibroblasts appeared unaltered compared to that of N13R10. However, following experimental challenge of immunocompromised guinea pigs, r129 induced significant weight loss, longer duration of viremia, and dramatically higher (up to 1.5 × 10(6)-fold) viral loads in blood and end organs compared to N13R10. In pregnant guinea pigs, challenge with doses of r129 virus of ≥5 × 10(6) PFU resulted in levels of maternal viremia, congenital transmission, pup viral loads, intrauterine growth restriction, and pup mortality comparable to that induced by pathogenic SG virus, although higher doses of r129 were required. These results suggest that the GP129-GP130 mutation is a significant contributor to attenuation of N13R10, likely by abrogating expression of a functional PC. IMPORTANCE: Tissue culture adaptation of cytomegaloviruses rapidly selects for mutations, deletions, and rearrangements in the genome, particularly for viruses passaged in fibroblast cells. Some of these mutations are focused in the region of the genome encoding components of the pentameric complex (PC), in particular homologs of human cytomegalovirus (HCMV) proteins UL128, UL130, and UL131A. These mutations can attenuate the course of infection when the virus is reintroduced into animals for vaccine and pathogenesis studies. This study demonstrates that a deletion that arose during the process of tissue culture passage can be repaired, with subsequent restoration of pathogenicity, using BAC-based mutagenesis. Restoration of pathogenicity by repair of a frameshift mutation in GPCMV gene GP129 using this approach provides a valuable genetic platform for future studies using the guinea pig model of congenital CMV infection.
[Mh] Termos MeSH primário: Infecções por Citomegalovirus/congênito
Infecções por Citomegalovirus/patologia
Fibroblastos/virologia
Mutação
Multimerização Proteica
Roseolovirus/genética
Roseolovirus/patogenicidade
[Mh] Termos MeSH secundário: Animais
Peso Corporal
Cromossomos Artificiais Bacterianos
Infecções por Citomegalovirus/virologia
Modelos Animais de Doenças
Escherichia coli/genética
Glicoproteínas/genética
Cobaias
Roseolovirus/crescimento & desenvolvimento
Deleção de Sequência
Inoculações Seriadas
Carga Viral
Proteínas Estruturais Virais/genética
Viremia
Virulência
Fatores de Virulência/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Glycoproteins); 0 (Viral Structural Proteins); 0 (Virulence Factors)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170714
[Lr] Data última revisão:
170714
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160617
[St] Status:MEDLINE
[do] DOI:10.1128/JVI.00320-16


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[PMID]:26973071
[Au] Autor:Cardin RD; Bravo FJ; Pullum DA; Orlinger K; Watson EM; Aspoeck A; Fuhrmann G; Guirakhoo F; Monath T; Bernstein DI
[Ad] Endereço:Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA. Electronic address: rhonda.cardin@cchmc.org.
[Ti] Título:Replication-defective lymphocytic choriomeningitis virus vectors expressing guinea pig cytomegalovirus gB and pp65 homologs are protective against congenital guinea pig cytomegalovirus infection.
[So] Source:Vaccine;34(17):1993-9, 2016 Apr 12.
[Is] ISSN:1873-2518
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Congenital cytomegalovirus infection can be life-threatening and often results in significant developmental deficits and/or hearing loss. Thus, there is a critical need for an effective anti-CMV vaccine. OBJECTIVE: To determine the efficacy of replication-defective lymphocytic choriomeningitis virus (rLCMV) vectors expressing the guinea pig CMV (GPCMV) antigens, gB and pp65, in the guinea pig model of congenital CMV infection. METHODS: Female Hartley strain guinea pigs were divided into three groups: Buffer control group (n = 9), rLCMV-gB group (n = 11), and rLCMV-pp65 (n = 11). The vaccines were administered three times IM at 1.54 × 10(6)FFU per dose at 21-day intervals. At two weeks after vaccination, the female guinea pigs underwent breeding. Pregnant guinea pigs were challenged SQ at ∼ 45-55 days of gestation with 1 × 10(5)PFU of GPCMV. Viremia in the dams, pup survival, weights of pups at delivery, and viral load in both dam and pup tissues were determined. RESULTS: Pup survival was significantly increased in the LCMV-gB vaccine group. There was 23% pup mortality in the gB vaccine group (p = 0.044) and 26% pup mortality in the pp65 vaccine group (p = 0.054) compared to 49% control pup mortality. The gB vaccine induced high levels of gB binding and detectable neutralizing antibodies, reduced dam viremia, and significantly reduced viral load in dam tissues compared to control dams (p < 0.03). Reduced viral load and transmission in pups born to gB-vaccinated dams was observed compared to pups from pp65-vaccinated or control dams. CONCLUSIONS: The rLCMV-gB vaccine significantly improved pup survival and also increased pup weights and gestation time. The gB vaccine was also more effective at decreasing viral load in dams and pups and limiting congenital transmission. Thus, rLCMV vectors that express CMV antigens may be an effective vaccine strategy for congenital CMV infection.
[Mh] Termos MeSH primário: Infecções por Citomegalovirus/prevenção & controle
Vacinas contra Citomegalovirus/imunologia
Fosfoproteínas/imunologia
Proteínas do Envelope Viral/imunologia
Proteínas da Matriz Viral/imunologia
[Mh] Termos MeSH secundário: Animais
Animais Recém-Nascidos
Anticorpos Neutralizantes/sangue
Anticorpos Antivirais/sangue
Infecções por Citomegalovirus/congênito
Feminino
Cobaias
Células HEK293
Seres Humanos
Vírus da Coriomeningite Linfocítica/fisiologia
Gravidez
Roseolovirus
Carga Viral
Replicação Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies, Neutralizing); 0 (Antibodies, Viral); 0 (Cytomegalovirus Vaccines); 0 (Phosphoproteins); 0 (Viral Envelope Proteins); 0 (Viral Matrix Proteins); 0 (cytomegalovirus matrix protein 65kDa); 0 (glycoprotein B, Simplexvirus)
[Em] Mês de entrada:1610
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160315
[St] Status:MEDLINE


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[PMID]:26079615
[Au] Autor:Swanson EC; Gillis P; Hernandez-Alvarado N; Fernández-Alarcón C; Schmit M; Zabeli JC; Wussow F; Diamond DJ; Schleiss MR
[Ad] Endereço:University of Minnesota Medical School, Department of Pediatrics, Center for Infectious Diseases and Microbiology Translational Research, 2001 6th Street SE, Minneapolis, MN 55455, United States.
[Ti] Título:Comparison of monovalent glycoprotein B with bivalent gB/pp65 (GP83) vaccine for congenital cytomegalovirus infection in a guinea pig model: Inclusion of GP83 reduces gB antibody response but both vaccine approaches provide equivalent protection against pup mortality.
[So] Source:Vaccine;33(32):4013-8, 2015 Jul 31.
[Is] ISSN:1873-2518
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Cytomegalovirus (CMV) subunit vaccine candidates include glycoprotein B (gB), and phosphoprotein ppUL83 (pp65). Using a guinea pig cytomegalovirus (GPCMV) model, this study compared immunogenicity, pregnancy outcome, and congenital viral infection following pre-pregnancy immunization with a three-dose series of modified vaccinia virus Ankara (MVA)-vectored vaccines consisting either of gB administered alone, or simultaneously with a pp65 homolog (GP83)-expressing vaccine. Vaccinated and control dams were challenged at midgestation with salivary gland-adapted GPCMV. Comparisons included ELISA and neutralizing antibody responses, maternal viral load, pup mortality, and congenital infection rates. Strikingly, ELISA and neutralization titers were significantly lower in the gB/GP83 combined vaccine group than in the gB group. However, both vaccines protected against pup mortality (63.2% in controls vs. 11.4% and 13.9% in gB and gB/GP83 combination groups, respectively; p<0.0001). Reductions in pup viral load were noted for both vaccine groups compared to control, but preconception vaccination resulted in a significant reduction in GPCMV transmission only in the monovalent gB group (26/44, 59% v. 27/34, 79% in controls; p<0.05). We conclude that, using the MVA platform, the addition of GP83 to a gB subunit vaccine interferes with antibody responses and diminishes protection against congenital GPCMV infection, but does not decrease protection against pup mortality.
[Mh] Termos MeSH primário: Infecções por Citomegalovirus/congênito
Infecções por Citomegalovirus/prevenção & controle
Vacinas contra Citomegalovirus/imunologia
Transmissão Vertical de Doença Infecciosa/prevenção & controle
Fosfoproteínas/imunologia
Roseolovirus/imunologia
Proteínas do Envelope Viral/imunologia
Proteínas da Matriz Viral/imunologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Neutralizantes/sangue
Anticorpos Antivirais/sangue
Infecções por Citomegalovirus/transmissão
Vacinas contra Citomegalovirus/administração & dosagem
Modelos Animais de Doenças
Ensaio de Imunoadsorção Enzimática
Feminino
Cobaias
Testes de Neutralização
Gravidez
Análise de Sobrevida
Resultado do Tratamento
Vacinas de Subunidades/administração & dosagem
Vacinas de Subunidades/imunologia
Carga Viral
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Antibodies, Neutralizing); 0 (Antibodies, Viral); 0 (Cytomegalovirus Vaccines); 0 (Phosphoproteins); 0 (Vaccines, Subunit); 0 (Viral Envelope Proteins); 0 (Viral Matrix Proteins); 0 (cytomegalovirus matrix protein 65kDa); 0 (glycoprotein B, Simplexvirus)
[Em] Mês de entrada:1604
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150617
[St] Status:MEDLINE


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[PMID]:25468809
[Au] Autor:Krug LT
[Ad] Endereço:Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794, USA. Electronic address: laurie.krug@stonybrook.edu.
[Ti] Título:Editorial overview: Roseoloviruses: stopping to smell the roses--the Roseoloviruses have come of age as human pathogens.
[So] Source:Curr Opin Virol;9:vi-vii, 2014 Dec.
[Is] ISSN:1879-6265
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Mh] Termos MeSH primário: Interações Hospedeiro-Patógeno
Infecções por Roseolovirus/patologia
Infecções por Roseolovirus/virologia
Roseolovirus/isolamento & purificação
Roseolovirus/fisiologia
[Mh] Termos MeSH secundário: Seres Humanos
Roseolovirus/patogenicidade
Infecções por Roseolovirus/epidemiologia
[Pt] Tipo de publicação:EDITORIAL; INTRODUCTORY JOURNAL ARTICLE
[Em] Mês de entrada:1508
[Cu] Atualização por classe:160520
[Lr] Data última revisão:
160520
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:141204
[St] Status:MEDLINE



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