Oncogenic Virus Epidemiology and Pathophysiology - CNRS URA 3015  


  HEADProf. Antoine Gessain / antoine.gessain@pasteur.fr
  MEMBERSBerthet Nicolas (Ingénieur), Betsem Edouard (Doctorant), Buseyne Florence (CR), Cassar Olivier (CR), Ceccaldi Pierre-Emmanuel (Prof. Univ Paris 7), Desdouits Marion (Doctorante), Desrames Alexandra (Etudiante M2), Filippone Claudia (Postdoc), Jeannin Patricia (Technicienne Supérieure), Martel-Jantin Claire (Doctorante), Mazalrey Simon (Technicien), Montange Thomas (Etudiant M2), Rua Réjane (Doctorante), Tortevoye Patricia (Ingénieur), Ziani Isma (Secrétaire)


  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 2010, 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, as well as HTLV-3, a novel human retrovirus, uncovered by our unit in 2005. We have also participated to the evaluation of a re-sequencing microarray for viral detection and characterization. Furthermore, a recent programm started on the novel human polyomavirus and the associated Merkel cell carcinoma.

1) Clinical and genetic epidemiology of HTLV-1 and HHV-8 in endemic areas (French Guyana, Gabon and Peru). 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 envand HHV-8 K1 gene were also conducted on a large series of viral strains from Siberia, Peru and Cameroon.

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 to gain better knowledge on the transmission of SFV to humans after contacts with Apes and monkeys. We also studied the genetic characterization of such zoonotic viruses present in Humans. 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. A specific study on an indeterminate HTLV Western blot serological pattern frequent in Central Africa was performed.

4) Studies on the mechanisms of mother-to-child transmission of HTLV-1. Using an in vitromodel of human intestinal epithelial barrier, we are working on the mechanisms of trans-epithelial passage of HTLV-1 to assess the respective role of para-cellular and trans-cellular passages. This study also includes the possible role of dendritic cells as targets of HTLV-1 infection after such a passage.

6) Study on the viral myosites. In order to delineate the main characteristics of HTLV-1–associated myosites, we have performed a virological, anatomopathological and immunological study on a dozen of HTLV-1-associated myosites cases. In parallel, we investigated the mechanisms of viral induced myosites in the case of influenza and Alphavirus (Chikungunya, Sindbis) infection. In particular, the sensibility of human primary muscle cells to these viruses and the effect of infection on muscle cell physiology is studied in vitro.

7) Lastly, the validation of a high density DNA resequencing microarray has continued and used in order to improve diagnosis and characterization of emerging pathogens. This was applied in 2009/2010 to influenza viruses (seasonal and pandemic H1N1 strains), to detection and characterization of highly pathogenic viruses (P4 agents) and arboviruses including 4 serotypes of dengue viruses and a large panel of Alphaviruses. The design of a novel generation of microarray containing over 800 viral sequences is in progress.

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

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



  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 2010 - Institut Pasteur
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