Oncogenic Herpesviruses

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Research themes

More than 90% of the adult human population is infected by Epstein-Barr virus (EBV). Infection takes place early in life and then persists life-long. EBV is the etiological agent of infectious mononucleosis (glandular fever or ‘kissing disease’), but most EBV carriers show no symptoms or pathology at the time of infection. However, EBV is strongly associated with a number of human tumors such as nasopharyngeal carcinoma, gastric cancer, Burkitt’s lymphoma, immunosuppression-related lymphomas, Hodgkin’s disease, and others. In addition, EBV is suspected to have a role in the development of various autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis or multiple sclerosis and is implicated in the chronic fatigue syndrome. 11% of viral associated human cancers are associated with EBV.

02_Equipe Manet_Figure1
EBV infects human B lymphocytes and certain epithelial cells in vitro and in vivo. After infection of resting B-lymphocytes, the virus reactivates the cells and induces their indefinite proliferation (immortalization) by establishing a latent infection (i.e. the cells do not release virus). The infected cells carry several copies of the EBV episome and express a subset of the viral genes (the so-called latent genes). These viral latent genes contribute to the induction and maintenance of B-cell proliferation. It is now well accepted that replication of EBV is an important step before the appearance of the pathologies.

In our lab, we are studying the mechanisms by which EBV induces B cells immortalization and the regulation of the switch between latent persistence and virus replication. We focus our study on the biological role of some key viral genes that contribute to these processes at the genetic, molecular and cellular levels.

Main achievements

  • Characterization of the viral transcription factor Rta (BRLF1).
  • Identification of the cellular protein ubinuclein (Ubn-1).
  • Determination of the role of the cellular protein RBPJ-k in the control of EBNA2 mediated gene expression.
  • Characterization of the viral early protein EB2 (SM). EB2 is required for nuclear mRNAs stability, cytoplasmic accumulation of intronless viral mRNAs and translation viral mRNAs.
  • Characterization of the viral TATA-binding protein like: BcRF1 a viral TBP-like protein
  • Identification of the full set of viral proteins required for viral late genes expression: a viral specific transcription pre-Initiation Complex (vPIC). Complex conserved in all β- and γ-herpesviruses but absent in α-herpesviruses

Sponsors

INSERM, ARC, Université, ANR, Ligue contre le Cancer, ANRS, FRM, CNRS.

 

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