Biology of viral emerging infections


  HEADDr TORDO Noël / ntordo@pasteur.fr
  MEMBERSDr BAIZE Sylvain / GALLAIS Fabrice / Dr MARIANNEAU Philippe / Dr PANNETIER Delphine / Dr SCHUFFENECKER Isabelle /Dr ZELLER Hervé


  Annual Report

The “Unité de Biologie des Infections Virales Emergentes” (UBIVE) is based in Lyon (IFR 128 Biosciences). UBIVE develops expertise in research, surveillance and diagnosis of Biosafety Level 4 and 3 (BSL4/3) viral agents and associated diseases (mostly zoonoses). UBIVE is hosting two National Reference Centres (NRC), on Arboviruses and Haemorrhagic Fevers, which are WHO Collaborative Centres (WHOCC) as well. All activities require access to BSL4/3 facilities of the Laboratory Jean Mérieux (directed by INSERM).

Research activities can be separated between projects originally developed at UBIVE or in collaboration with other teams looking for a unique BSL4 expertise. Lassa virus (LV) is currently the basic model of UBIVE. It is transmitted to human by contact with the Mastomys sp reservoir, but human-to-human transmission may also occur. Pathogenesis in human varies from asymptomatic infection to fatal haemorrhagic fever (5,000 deaths/year in West Africa). Macrophages and endothelial cells are the main targets. Mopeia virus (MV) is closely related to LV but non pathogenic for humans and non-human primates. To understand the molecular basis of pathogenesis, we compare immune responses induced by LV and MV. MV infection of dendritic cells and macrophages leads to a robust release of chemokines and type I IFN, while LV infection does not. This lack of cellular activation by LV could explain the uncontrolled viral replication and the immunosuppression observed in severe cases. In addition, infection of dendritic cells by MV and LV induce strong and weak T cell responses (helper and cytotoxic), respectively, further consistent with their respective attenuated and pathogenic phenotypes.

Various animal models reproducing BSL3/4 virus infections have been developed: primates (Saimiri, macaque) for LV, Nipah virus and West Nile (WN) virus; hamster and mouse KO for type 1 IFN receptor for LV and SARS. These models have been used to test various vaccine candidates. One developed at UBIVE: a chimeric Yellow Fever – LV vaccine (insertion of the GP1-GP2 gene of LV into a 17D Yellow Fever virus genome backbone). The others in collaboration: candidate vaccines against SARS, chimeric measles – WN virus vaccine, (insertion of the E protein gene of WN virus into measles virus genome backbone).

NRC-WHOCC host collections of viral species and reagents. They need strict BSL3/4 containment to perform medical diagnosis (>4000/year) and expertise (survey or outbreaks) using antigenic, genetic methods and virus isolation. Recent features were a constant progress of Dengue and WN viruses and an unprecedented epidemic of Chickungunya virus in the Indian Ocean (2005-2006). Specific viral mutations in the Chikungunya genome could explain differential pathogenicity during the outbreak.

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  Publications

Publications 2006 of the unit on Pasteur's references database




Activity Reports 2006 - Institut Pasteur
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