Our group works on the human oncogenic retroviruses HTLV-1/HTLV-2 and the human herpesvirus HHV8 and on their simian related counterparts. During year 2001, 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 and adult T cell leukemia) and neurological associated diseases (tropical spastic paraparesis).

The recent Unit of Epidemiology and Physiopathology of Oncogenic Viruses has developed the following projects.

1. Epidemiology of the Human Herpes Virus 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.
2. Molecular epidemiology and genetic variability of HTLV-1/2 and related simian retroviruses (STLV-1/2). We have partially sequenced more than 30 new STLV-1 strains originating from Africa and South East Asia. Furthermore, the complete sequence (8919 bp) of a novel, highly divergent, STLV has 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.
3. Genetic variability of HHV8 and related simian viruses. We have discovered and partially characterized a novel HHV8 related virus in Chimpanzees living in Central Africa.
4. 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 characterisation and the use of a novel lentiviral vector containing the tax gene.
5. Mechanism of resistance to apoptosis of the HTLV-1 infected cells. These studies are currently in progress. We are dissecting, in vivo and in vitro, the mechanisms of action of several chemicals that could be used for the treatment of the HTLV-1 associated Adult T Cell Leukemia.
6. Studies regarding the phenotypic differences between the Tax proteins of HTLV-2 molecular subtypes A and B are ongoing. In particular, our group study the mechanisms of inactivation of the p53 tumor suppressor gene.
7. 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. Our results strenghten the potential oncogenic properties of HHV8 in vivo.

For most of these studies, the collaboration with numerous colleagues and friends of the Network of the Institut Pasteur and Instituts associés (especially Cameroon, Central African Republic and French Guyana) has been crucial.

Mahieux Renaud, INSERM, Chargé de Recherche, rmahieux@pasteur.fr

Quere Nelly, stagiaire ESTBA

Van Beveren Monique, Assistant Ingénieur, CNRS