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1.
PLoS Pathog ; 5(7): e1000506, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19578441

RESUMO

The genome of Epstein-Barr virus (EBV) encodes 86 proteins, but only a limited set is expressed in EBV-growth transformed B cells, termed lymphoblastoid cell lines (LCLs). These cells proliferate via the concerted action of EBV nuclear antigens (EBNAs) and latent membrane proteins (LMPs), some of which are rate limiting to establish a stable homeostasis of growth promoting and anti-apoptotic activities. We show here that EBV mutants, which lack the EBNA-3A gene, are impaired but can still initiate cell cycle entry and proliferation of primary human B cells in contrast to an EBNA-2 deficient mutant virus. Surprisingly, and in contrast to previous reports, these viral mutants are attenuated in growth transformation assays but give rise to permanently growing EBNA-3A negative B cell lines which exhibit reduced proliferation rates and elevated levels of apoptosis. Expression profiles of EBNA-3A deficient LCLs are characterized by 129 down-regulated and 167 up-regulated genes, which are significantly enriched for genes involved in apoptotic processes or cell cycle progression like the tumor suppressor gene p16/INK4A, or might contribute to essential steps of the viral life cycle in the infected host. In addition, EBNA-3A cellular target genes remarkably overlap with previously identified targets of EBNA-2. This study comprises the first genome wide expression profiles of EBNA-3A target genes generated within the complex network of viral proteins of the growth transformed B cell and permits a more detailed understanding of EBNA-3A's function and contribution to viral pathogenesis.


Assuntos
Linfócitos B/fisiologia , Linfócitos B/virologia , Antígenos Nucleares do Vírus Epstein-Barr/biossíntese , Herpesvirus Humano 4/genética , Linfócitos B/imunologia , Linfócitos B/metabolismo , Linhagem Celular , Proliferação de Células , Análise por Conglomerados , Antígenos Nucleares do Vírus Epstein-Barr/genética , Perfilação da Expressão Gênica/métodos , Herpesvirus Humano 4/crescimento & desenvolvimento , Herpesvirus Humano 4/metabolismo , Humanos , Ativação Linfocitária , Análise de Sequência com Séries de Oligonucleotídeos , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa
2.
Cell Mol Life Sci ; 67(24): 4249-56, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20593215

RESUMO

Epstein-Barr virus (EBV) is a human gamma herpes virus that infects B cells and induces their transformation into immortalized lymphoblasts that can grow as cell lines (LCLs) in vitro. EBNA-3 is a member of the EBNA-3-protein family that can regulate transcription of cellular and viral genes. The identification of EBNA-3 cellular partners and a study of its influence on cellular pathways are important for understanding the transforming action of the virus. In this work, we have identified the vitamin D receptor (VDR) protein as a binding partner of EBNA-3. We found that EBNA3 blocks the activation of VDR-dependent genes and protects LCLs against vitamin-D3-induced growth arrest and/or apoptosis. The presented data shed some light on the anti-apoptotic EBV program and the role of the EBNA-3-VDR interaction in the viral strategy.


Assuntos
Antígenos Nucleares do Vírus Epstein-Barr/metabolismo , Regulação da Expressão Gênica , Herpesvirus Humano 4/metabolismo , Receptores de Calcitriol/metabolismo , Animais , Calcifediol/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Antígenos Nucleares do Vírus Epstein-Barr/genética , Herpesvirus Humano 4/genética , Humanos , Linfócitos/citologia , Linfócitos/fisiologia , Espectrometria de Massas , Receptores de Calcitriol/genética
3.
Berl Munch Tierarztl Wochenschr ; 124(1-2): 8-16, 2011.
Artigo em Alemão | MEDLINE | ID: mdl-21309162

RESUMO

Within the framework of a cooperative research project, turkey health as well as numerous aspects of animal welfare were examined in various intensive commercial farms with varying rearing forms. The present study demonstrates the prevalence of skin injuries concerning living animals as well as carcasses of slaughtered turkeys of both sexes. Although all turkeys were debeaked, prevalences of skin injuries at a value of 12.8% with male turkeys and 13.8% with female turkeys could be found at the age of 16 weeks. Within the scope of medically inspections skin injuries were mainly established in the head region, especially the snood as well as in the region of the back. By means of their clinical picture pecking wounds and scratch injuries could be distinguished. Skin lesion produced primary as a result of scratching the skin surface, could be enlarged by the animal itself or by conspecifics by beak pecking, especially after bleeding, in spite of debeaked upper beak. Injuries in the head region, especially of the snood, could be explained mainly as a result of pecking by conspecifics by reason of their clinical picture and were found mainly in male turkeys. Skin injuries in the region of the back, especially at the coxal tuberosity, were identified primarily as scratch marks. They were found mainly in female turkeys. A statistically significant correlation of the injury prevalence to particular husbandry parameters discussed in the literature as "predisposing" or "limiting" factors (e.g., population density, light regime or offer of employment material) could not be established in this study. At the meat inspection fresh scratching injuries at the chest and the hind legs were diagnosed most often. Especially fresh injuries of the carcass point to a misguided behaviour of the staff concerning animal handling during loading and transport which is not conform to animal welfare.


Assuntos
Bico/cirurgia , Pele/lesões , Perus/lesões , Bem-Estar do Animal , Animais , Dorso , Feminino , Cabeça , Masculino , Fatores Sexuais , Pele/patologia , Perus/cirurgia , Ferimentos e Lesões/epidemiologia , Ferimentos e Lesões/patologia , Ferimentos e Lesões/veterinária
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