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EBV persistence without its EBNA3A and 3C oncogenes in vivo.
Murer, Anita; McHugh, Donal; Caduff, Nicole; Kalchschmidt, Jens; Barros, Mario; Zbinden, Andrea; Capaul, Riccarda; Niedobitek, Gerald; Allday, Martin; Chijioke, Obinna; Münz, Christian.
Afiliação
  • Murer A; Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland.
  • McHugh D; Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland.
  • Caduff N; Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland.
  • Kalchschmidt J; Genomics and Immunity, NIAMS, National Institutes of Health, Bethesda, MD, United States of America.
  • Barros M; Institute of Pathology, Unfallkrankenhaus Berlin, Berlin, Germany.
  • Zbinden A; Institute of Medical Virology, University of Zürich, Zürich, Switzerland.
  • Capaul R; Institute of Medical Virology, University of Zürich, Zürich, Switzerland.
  • Niedobitek G; Institute of Pathology, Unfallkrankenhaus Berlin, Berlin, Germany.
  • Allday M; Molecular Virology, Department of Medicine, Imperial College London, London, United Kingdom.
  • Chijioke O; Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland.
  • Münz C; Institute of Pathology and Molecular Pathology, University Hospital Zürich, Zürich, Switzerland.
PLoS Pathog ; 14(4): e1007039, 2018 04.
Article em En | MEDLINE | ID: mdl-29709016
ABSTRACT
The oncogenic Epstein Barr virus (EBV) infects the majority of the human population and usually persists within its host for life without symptoms. The EBV oncoproteins nuclear antigen 3A (EBNA3A) and 3C (EBNA3C) are required for B cell transformation in vitro and are expressed in EBV associated immunoblastic lymphomas in vivo. In order to address the necessity of EBNA3A and EBNA3C for persistent EBV infection in vivo, we infected NOD-scid γcnull mice with reconstituted human immune system components (huNSG mice) with recombinant EBV mutants devoid of EBNA3A or EBNA3C expression. These EBV mutants established latent infection in secondary lymphoid organs of infected huNSG mice for at least 3 months, but did not cause tumor formation. Low level viral persistence in the absence of EBNA3A or EBNA3C seemed to be supported primarily by proliferation with the expression of early latent EBV gene products transitioning into absent viral protein expression without elevated lytic replication. In vitro, EBNA3A and EBNA3C deficient EBV infected B cells could be rescued from apoptosis through CD40 stimulation, mimicking T cell help in secondary lymphoid tissues. Thus, even in the absence of the oncogenes EBNA3A and 3C, EBV can access a latent gene expression pattern that is reminiscent of EBV persistence in healthy virus carriers without prior expression of its whole growth transforming program.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos B / Herpesvirus Humano 4 / Antígenos Nucleares do Vírus Epstein-Barr / Infecções por Vírus Epstein-Barr Limite: Animals / Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos B / Herpesvirus Humano 4 / Antígenos Nucleares do Vírus Epstein-Barr / Infecções por Vírus Epstein-Barr Limite: Animals / Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article