Unit: Oncogenic Virus Epidemiology and Pathophysiology

Director: GESSAIN Antoine

Our group works on the human oncogenic retroviruses HTLV-1/HTLV-2 and on the human herpesvirus HHV-8 and their simian related counterparts. During the year 2004, we have continued ongoing projects and developed new studies on both 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 Unit of Epidemiology and Physiopathology of Oncogenic Viruses has developed the following projects.

Epidemiology of the Human Herpesvirus 8 (HHV-8) 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, especially in a large cohort of pregnant women.

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 from Central Africa. These data strenghten the hypothesis of interspecies transmission from STLV-1, present in monkeys, to humans especially in Central Africa leading to the foci of HTLV-1 in some human population of these regions. 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. We also continue our studies on the signification of HTLV-1/2 indeterminate serologies.

Genetic variability of HHV-8 and related simian gamma herpesviruses. In particular we have studied 35 novel HHV-8 sequences from Marocco patients suffering of Kaposi's sarcoma and we have characterized novel β and γ simians herpesviruses strains.

Studies on the pathogenesis of HTLV-1 have also been performed. This 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 in vitro and ex vivo 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 on their intra-cellular localization.

In vivo clonality of HHV-8 associated diseases. Studies are 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 HHV-8 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, herpesviruses, epidemiology, genetic variability, pathogenesis

Activity Reports 2004 - Institut Pasteur

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