Oncogenic Virus Epidemiology and Pathophysiology - CNRS URA1930  


  HEADDr GESSAIN Antoine / agessain@pasteur.fr
  MEMBERSABOUT Frédégonde / AFONSO Philippe / Dr CALATTINI Sara / CASSAR Olivier
Dr CECCALDI Pierre Emmanuel / CHEVALIER Sébastien / GESSAIN Antoine / Dr KO Thérésa Nga Ling
Dr MAHIEUX Renaud / Dr OZDEN Simona / TORTEVOYE Patricia


  Annual Report

Our work concerns mainly the human oncogenic retrovirus HTLV-1 and the human herpesvirus 8 (HHV-8). In 2006, we have developed several studies both on the clinical and molecular epidemiology of these viruses and on the physiopathology of the tumoral (Kaposi's sarcoma, adult T cell leukemia) and inflammatory associated diseases (tropical spastic paraparesis-TSP/HAM and myositis). We have also studied emerging viruses including: Chikungunya and its associated myalgias, simian and human foamy-viruses and HTLV-3, a novel retrovirus, that our unit discovered in 2005.

Epidemiology of HTLV-1 and HHV-8 in endemic areas: French Guyana, central Africa and Melanesia. These long-term projects are aimed at searching how these viruses are transmitted within family and whether a host genetic susceptibility to infection with such viruses is present, especially in children. Genetic variability studies on the HHV-8 K1 gene in a large series of novel viral strains from Morocco, South America and Oceania was also conducted.

Molecular epidemiology of HTLV-1/2/3 and related simian retroviruses (STLV) in central Africa. Our findings strengthen the hypothesis of interspecies transmission from STLV-1/3, present in monkeys, to humans, leading to foci of HTLV-1/3.

Signification of HTLV-1/2 indeterminate serologies and discovery of a new human retrovirus. In 2005, we discovered in Cameroon, a new retrovirus HTLV-3. It is closely related to STLV-3. We are now studying its geographical distribution in different areas and populations of central Africa as well as the mechanisms/factors that lead to such interspecies transmission.

Molecular characterization of HTLV-3. Although HTLV-3 and HTLV-1 have only 60% identity, we demonstrated that the human Tax3 protein is closely related to the transforming protein Tax1. This led us to suggest that HTLV-3, like HTLV-1, might be pathogenic in vivo. Construction of molecular clones of both HTLV-3 and STLV-3 are in progress.

Studies on the pathogenesis of HTLV-1. This includes viro-molecular studies of the central nervous system from patients suffering of TSP/HAM. We also developed studies aiming at better understanding the role of the Tax1 protein in the pathogenesis of the HTLV-1 associated myositis. The role of activated HTLV-1 infected lymphocytes in the alteration of the blood brain barrier was also studied, as well as the role of DC-SIGN in the facilitation of the fusion of dendritic cells with HTLV-1 infected cells

In vivo clonality of HHV-8 associated diseases. Studies were focused on the different forms and on the multi-focal aspects of Kaposi’s sarcoma. Our goal is to understand the role of latent HHV-8 infection in the development of such tumors in vivo.

For most of these studies, the collaboration with several colleagues of the Network of the Institut Pasteur and Instituts associés, as well as with several clinicians from Paris Hospitals has been crucial.

gessain.jpg

Interactions of a dendritic cell with an HTLV-1 infected lymphocyte



  Publications

Publications 2006 of the unit on Pasteur's references database




Activity Reports 2006 - Institut Pasteur
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