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Centre d'Immunologie et des Maladies Infectieuses
UPMC UMRS CR7 - Inserm U1135 - CNRS ERL 8255

Persistent Viral Infections - Dina Kremsdorf & Vincent Maréchal (Interim)

Team members

Team research program

The research interest of our team is in pathogenesis and therapy of persistent viral infections (PVIs), with a particular emphasis on three DNA viruses of high medical interest, hepatitis B virus (HBV), and two herpesviruses, Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6).

Hepatitis B virus (HBV)

The direct contribution of HBV infection to cirrhosis and hepatocellular carcinoma is addressed with a specific focus on the role of viral proteins HBx, HBSP and HBs. Investigations are performed both on infected cohort clinical level, on murine models and in vitro, on hepatocytes cultures.

Epstein-Barr virus (EBV)

Research aims to enhance our insight into molecular and cellular mechanisms related to genesis and genesis and development of EBV-associated lymphomas. We are concentrating on role of the circulating alarmin HMGB1 in this process and on its effect during EBV infection and the following cellular modifications.

Human Herpesvirus- 6 (HHV-6)

The chromosomal integration of HHV-6 DNA (ciHHV-6) constitutes a unique form of latency among human herpesviruses. The possible pathophysiological consequences of ciHHV-6 are investigated during pregnancy and in organ transplant patients. The ability of ciHHV-6 to reactivate in response to the microenvironment of infected cells is studied in vitro and correlated with the occurrence of drug induced reactivations observed in patients.

The susceptibility of EBV and HHV-6 to nucleoside/nucleotide analogues is measured thanks to appropriate monitoring tests in vivo and susceptibility assays in vitro. We are exploring a correlation between variability of response to therapy and specific alterations of target viral genes (through the analysis of selected mutants obtained in vitro as well as primary isolates from patients experiencing therapeutic failure). Innovative therapies will be tested, based on the association between specific antiviral inhibitors and drugs modulating cell gene expression, such as histone deacetylase inhibitors, which might act as modulators of virus reactivation.

Technical expertise

  • Molecular and serologic diagnosis of herpesvirus and HBV infections
  • Molecular biology techniques (PCR, RT-PCR, sequencing, cloning, expression, computer analysis) applied to the study of viral genomes and transcripts
  • Phenotypic and genetic assays for the determination of susceptibility or resistance to antivirals
  • Transgenic mouse models of HBV infection

Main achievements

  • Characterization of the resistance of HHV-6 and HSV antiviral inhibitors of DNA polymerases
  • Analysis of the genetic variability of HHV-6 and HSV with identification of major variants: the two species, HHV-6A and HHV-6B, HHV-6; a major variant of HSV-2 and HIV-related West African present

External funding (current)

ANRS (2015-2017) : Etude in vivo des conséquences de la variabilité générique de la protéine HBx du virus de l'hépatite B sur la pathogénèse hépatique
ANRS (2016-2018) :  Protéine HBSP du virus de l'hépatite B et réponse immunitaire
Ligue contre le cancer (2017) : Mutants naturels de la protéine HBx du virus de l'hépatite B

Publications (PDF):

(2017 - 2016 - 2015 - 2014 - 2013)

20/11/17

Traductions :

Contact

cimi-paris @ upmc.fr

To see

Key words

Medical virology; Persistent virus infection (PVI), Innate immunity, Cancer and inflammation

Fields of application

Diagnostic and serological markers of PVI; Antiviral therapy of PVI; Detection and quantification of acquired resistance to therapies against PVIs