Oncogenic Virus Epidemiology and Pathophysiology - CNRS URA 3015  


  HEADAntoine Gessain / gessain@pasteur.fr
  MEMBERSGessain Antoine Lab Head, Unit Head, HDR Institut Pasteur / Ozden Simona Lab Head, équivalent HDR Institut Pasteur / Ceccaldi Pierre-Emmanuel Chargé de Recherche, HDR Institut Pasteur/ Mahieux Renaud Chargé de Recherche 1, HDR Inserm
Afonso Philippe PhD Thesis 3rd Year Ministry Fellowship/ Berthet Nicolas Post Doc/ Betsem A Betsem Edouard PhD Thesis 1st Year (50 %) Bourse Egide/ Blaudin de Thé Guy Directeur Rech Emerite CNRS/ Cassar Olivier PhD Thesis 4th Year Institut Pasteur/ Desdouits Marion M 2
Douceron Estelle M 2/ Journo Chloé PhD Thesis 1st Year ENS Paris/ Ko Thérésa Post Doc Croucher Foundation/ Martin-Latil Sandra Post Doc Financement ANR/ Plancoulaine Sabine Chargé de Recherche 1 (10 %) Inserm
Tortevoye Patricia Engineer Institut Pasteur/ Bassot Sylviane Technician Institut Pasteur/ Joseph Bosco Lab Agent (25 %) Institut Pasteur/ Creff Jocelyne Lab Agent (25 %) Institut Pasteur/ Ziani Isma Secretary (25 %) Institut Pasteur


  Annual Report

Our work is mainly focused on the human oncogenic retrovirus HTLV-1 as well as on the human herpesvirus 8 (HHV-8). In 2007, we developed several studies, both on the clinical and molecular epidemiology of these viruses and on the physiopathology of the tumoral (Adult T cell leukemia, Kaposi's sarcoma) and on the 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 human 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 genetic susceptibility factor to infection with such viruses is present, especially among children. Genetic variability studies on the HTLV-1 envand HHV-8 gene in a large series of novel viral strains from Melanesia were also conducted.

Molecular epidemiology of HTLV-1/2/3 and their related simian retroviruses (STLV) in central Africa.Our findings strengthen the hypothesis of interspecies transmission from STLV-1/3 that are 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 human retrovirus that was named HTLV-3. HTLV-3 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 Tax 1 transforming protein. 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 to address this question.

Studies on the pathogenesis of HTLV-1. This includes viro-molecular studies of the central nervous system from patients suffering of TSP/HAM and the role of activated HTLV-1 infected lymphocytes in the alteration of the blood brain barrier. We are also developing studies on viral myositis, such as the role of the viral Tax 1 protein in the pathogenesis of HTLV-1-associated myositis, as well as identifying the muscle satellite cells as targets of Chikungunya infection.

In vivoclonality 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 the latent HHV-8 infection in the development of such tumors in vivo.

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

Keywords: HTLV, HHV-8, Viral pathogenesis, Cell transformation, Genetic variability, Epidemiology

Epivironc.jpg

Detection of Chikungunya viral antigens in satellite muscle cells in a biopsy from a patient with myositis (from Ozden, Huerre et al., PLOS One; 2006).



  Publications

1) Meertens L, Chevalier S, Weil R, Gessain A, Mahieux R. A 10-amino acid domain within human T-cell leukemia virus type 1 and type 2 tax protein sequences is responsible for their divergent subcellular distribution. J Biol Chem. 2004 Oct 8;279(41):43307-20.

2) Calattini S, Chevalier SA, Duprez R, Bassot S, Froment A, Mahieux R, Gessain A. Discovery of a new human T-cell lymphotropic virus (HTLV-3) in Central Africa. Retrovirology. 2005 May 9;2(1):30.

3) Afonso PV, Ozden S, Prevost MC, Schmitt C, Seilhean D, Weksler B, Couraud PO, Gessain A, Romero IA, Ceccaldi PE.Human blood-brain barrier disruption by retroviral-infected lymphocytes: role of myosin light chain kinase in endothelial tight-junction disorganization. J Immunol. 2007 Aug 15;179(4):2576-83.  

4) Duprez R, Lacoste V, Brière J, Couppié P, Frances C, Sainte-Marie D, Kassa-Kelembho E, Lando MJ, Essame Oyono JL, Nkegoum B, Hbid O, Mahé A, Lebbé C, Tortevoye P, Huerre M, Gessain A. Evidence for a multiclonal origin of multicentric advanced lesions of Kaposi sarcoma. J Natl Cancer Inst. 2007 Jul 18;99(14):1086-94.

5) Ozden S, Huerre M, Riviere JP, Coffey LL, Afonso PV, Mouly V, de Monredon J, Roger JC, El Amrani M, Yvin JL, Jaffar MC, Frenkiel MP, Sourisseau M, Schwartz O, Butler-Browne G, Desprès P, Gessain A, Ceccaldi PE. Human muscle satellite cells as targets of Chikungunya virus infection. PLoS ONE. 2007 Jun 13;2(6):e527.





Activity Reports 2007 - Institut Pasteur
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