Oncogenic Virus Epidemiology and Pathophysiology - CNRS URA 3015  


  HEAD Prof. Antoine GESSAIN / antoine.gessain@pasteur.fr
  MEMBERSBassot Sylviane / Belhassen Chantal / Berthet Nicolas / Betsem Edouard / Cassar Olivier / Ceccaldi Pierre Emmanuel / Creff Jocelyne . Desdouits Marion / Desrames Alexandra / Filippone Claudia / Martel-Jantin Claire / Ozden Simona / Plancoulaine Sabine / Rua Réjane / Tortevoye Patricia / Ziani Isma


  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 myopathies, simian and human foamy-viruses, and HTLV-3, a novel human retrovirus, that our unit discovered in 2005. We have also recently participated to the developpement of a re-sequencing microarray for viral detection and characterization.

1) 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 and different central African population.

2) Clinical and 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-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 a better knowledge on the transmission of SFV to humans after contacts with Apes and monkeys. This will help us to understand the early events of retroviral emergence in humans.

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

4) 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. We also worked on the receptor of this new human retrovirus.

5) Studies on the pathogenesis of HTLV-1. This includes viro-molecular studies of the central nervous system (CNS) from patients suffering of TSP/HAM and the role of activated HTLV-1 infected lymphocytes in blood brain barrier alteration and mechanisms of HTLV-1 passage towards CNS.

6) Studies on the viral myositis. After studying the role of the viral Tax 1 protein in the pathogenesis of HTLV-1 associated myositis , we are also working on the physiopathology of the myositis associated with Chikungunya, other Alphaviruses.

7) Lastly, we have validated the use of a high density DNA re-sequencing microarray in order to improve diagnosis and characterization of emerging pathogens. This was specially applied in 2009 to influenza viruses (including H1N1 strain) and rhabdoviruses.

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



  Publications

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. Journal of the National Cancer Institute. 2007 Jul 18;99(14):1086-94.

Calattini S, Betsem EB, Froment A, Mauclère P, Tortevoye P, Schmitt C, Njouom R, Saib A, Gessain A. Simian foamy virus transmission from apes to humans, rural Cameroon. Emerging Infectious Diseases. 2007 Sep;13(9):1314-20.

Afonso PV, Ozden S, Cumont MC, Seilhean D, Cartier L, Rezaie P, Mason S, Lambert S, Huerre M, Gessain A, Couraud PO, Pique C, Romero IA. Alteration of blood-brain barrier integrity by retroviral infection. PLoS Pathogens. 2008 Nov;4(11):e1000205.

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. Journal of Infectious Diseases. 2009 Feb 15;199(4):561-4.

Berthet N, Leclerc I, Dublineau A, Shigematsu S, Burguière AM, Filippone C, Gessain A, Manuguerra JC. High-density resequencing DNA microarrays in public health emergencies. Nature Biotechnology. 2010 ; 28:1





Activity Reports 2009 - Institut Pasteur
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