Unit: Oncogenic Virus Epidemiology and Pathophysiology
Director: GESSAIN Antoine
Our group works on the human oncogenic retroviruses HTLV-1/HTLV-2 and the human herpesvirus HHV8 and their simian related counterparts. During year 2003, we have continued ongoing projects and developed new studies both on the clinical, analytical and molecular epidemiology of these viruses and on the physiopathology of the tumoral (Kaposi's sarcoma, adult T cell leukemia and primary effusion lymphoma) and inflammatory associated diseases (tropical spastic paraparesis and myositis).
The recent Unit of Epidemiology and Physiopathology of Oncogenic Viruses has developed the following projects.
Epidemiology of the Human Herpesvirus 8 (HHV8) and of the Human T Cell Leukemia Virus type 1 (HTLV-1) in endemic areas of French Guyana and Cameroon (Central Africa). These long term projects concern the intra-familial modes of transmission of these oncogenic viruses and the search for an host genetic susceptibility for acquiring such viruses. Other epidemiological studies regarding HTLV-1 and its associated diseases (Adult T cell leukemia and Tropical spastic paraparesis/HTLV-1 associated myelopathy) are also in progress in French Guyanese populations.
Molecular epidemiology and genetic variability of HTLV-1/2 and related simian retroviruses (STLV-1/2). We have partially sequenced (env gene and LTR region) more than 20 new STLV-1 strains originating mostly from South-East Asia but also central Africa. These data confort the hypothesis, especially in Central Africa, of interspecies transmission from STLV-1, present in monkeys, to humans leading to the foci of HTLV-1 in some human population of these regions. Furthermore, the complete sequences of two novel, highly divergent, STLV-3 have been obtained. Lastly a large epidemiological study on HTLV-2 infection is ongoing both at a clinical and at a molecular level in various ethnic populations living in a rain forest area of South Cameroon.
Genetic variability of HHV8 and related simian gamma herpesviruses. We have especially studied more than 30 novel HHV8 sequences from Russian patients with Kaposi's sarcoma and characterized novel β and γsimians herpesviruses.
Studies on the pathogenesis of HTLV-1 have also been performed. This mainly includes viro-molecular studies of the central nervous system and of muscular lesions in patients suffering of TSP/HAM as well as the development of studies aiming to better understand the role of the Tax protein in the pathogenesis of the polymyositis and inclusion body myositis associated with HTLV-1.
Comparative analysis of the mechanism of oncogenesis mediated by the Tax protein of HTLV-1 and HTLV-2. We are especially studying the interaction of these proteins with the tumor suppressor p53. We are also developing projects regarding the phenotypic differences between the Tax proteins of HTLV-1 and HTLV-2 as well as their intra-cellular localization.
In vivo clonality of HHV8 associated diseases. Studies are mainly focused on the different forms of Kaposi's sarcoma and on the multifocal aspects of such disease as well as on the primary effusion lymphomas. Our results strenghten the potential oncogenic properties of HHV8 in vivo.
For most of these studies, the collaboration with numerous colleagues of the Network of the Institut Pasteur and Instituts associés (especially Cameroon, Central African Republic and French Guyana) has been crucial.
Keywords: Retroviruses, HTLV, STLV, herpesviuses,epidemiology, genetic variability,pathogenese