Oncogenic Virus Epidemiology and Pathophysiology - CNRS URA 3015  


  HEADAntoine Gessain / antoine.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 CNRS / Betsem Edouard PhD Thesis 2nd Year (50 %) Bourse Egide / Blaudin de Thé Guy Directeur Rech. Emerite (10 %) CNRS / Blondot Marie-Lise M2 (20 %) Cassar Olivier Engineer Post Doc Institut Pasteur / Desdouits Marion PhD Thesis 1st Year ENS Paris / Douceron Estelle PhD Thesis 1st Year Ministry Fellowship / Galioot Amandine M2 (30 %) / Journo Chloé PhD Thesis 2st Year ENS Paris / Ko Thérésa Post Doc (80 %) Croucher Foundation / Martin-Latil Sandra Post Doc (80 %) 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 2008, we have 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 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, Gabon and South America). These long-term projects will allow us to determine how these viruses are transmitted within families and whether a susceptibility factor to infection with such viruses is present, especially among children. Genetic variability studies on the HTLV-1 env and HHV-8 K1gene were also conducted on a large series of viral strains from Siberia and South America.

Clinical andMolecular epidemiology of HTLV-1/2/3 and their related simian retroviruses (STLV) in central AfricaOur findings strengthen the hypothesis of interspecies transmission from STLV-3, as well as simian foamy viruses (SFV), to humans, leading to foci of HTLV-3 and presence of foamy viruses in human population. We continue to develop studies aimed at gaining abetter knowledge on the transmission of SFV to humans after severe bites from This will help us to understand the early events of retroviral emergence in humans.

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. More recently, we have discovered and characterized another strain of HTLV-3 .

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 . Molecular clones of both HTLV-3 and STLV-3 have been constructed 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 blood brain barrier alteration.

Studies on the viral myositis. We are also developing studies on viral myositis. We want to define the role of the viral Tax 1 protein in the pathogenesis of HTLV-1-associated myositis. We are also developing studies on Chikungunya and other alpha-viruses associated with myositis.

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

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

Epivironc.jpg

Syncytium formed by cultured brain endothelial cells (nuclei stained in blue) infected by HTLV-1 (viral protein p24 stained in green) From Afonso et al., Plos Pathogens, 2008.



  Publications

1) 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.

2) 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.

3) 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.

4) Afonso PV, Ozden S, Cumont MC, Seilhean D, Cartier L, Rezaie P, Mason S, Lambert S, Huerre M, Gessain A, Couraud PO, Pique C, Ceccaldi PE, Romero IA. Alteration of blood-brain barrier integrity by retroviral infection. PLoS Pathog. 2008 Nov;4 (11).

5) Calattini S, Betsem E, Bassot S, Chevalier SA, Mahieux R, Froment A, Gessain A New Strain of Human T Lymphotropic Virus (HTLV) Type 3 in a Pygmy from Cameroon with Peculiar HTLV Serologic Results.. J Infect Dis. 2008 Dec 19.





Activity Reports 2009 - Institut Pasteur
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