Viral Populations and Pathogenesis - CNRS URA 3015  


  HEADDr. Marco VIGNUZZI / marco.vignuzzi@pasteur.fr
  MEMBERSAna DE CASAS, administrative assistant Stéphanie BEAUCOURT, technician Dr. Lark COFFEY, postdoctoral fellow Laura LEVY, Master 2 candidate Nina GNÄDIG, Ph.D. candidate Jason KAELBER, undergraduate visiting student


  Annual Report

Our group is studying the behaviour of RNA viruses as populations during the course of an infection. Like any population of organisms, a virus population interacts with, reacts to, influences and is influenced by the environment it inhabits. We are interested in following the population dynamics and fluctuation of an RNA virus population as it enters the “virgin” territory of a new host and is eventually transmitted from this host during infection. When a host is infected, relatively few virus particles form the founding population that replicates, expands and disseminates during systemic infection. This expanding population encounters numerous environmental changes and challenges that include physical/anatomical barriers, tissue specific environments and the innate and adaptive immune responses. The arms race that occurs between virus and host environment influences the population structures that are eventually transmitted to new hosts, either naive or immune. Using new tools and technologies, we hope to identify the points during infection when the virus population is either most fragmented, most restricted or most heavily challenged by environmental pressure – target points for antiviral approaches.

Our tools

Using a combination of cell culture techniques and genetic manipulation of virus populations, we are generating virus populations presenting different degrees of genetic diversity with which to study virus fitness, evolution and pathogenesis in vivo. These approaches will be coupled to new sequencing technologies to better characterize virus populations and to develop new antiviral strategies. The viruses we use as study models, include Coxsackie virus, Chikungunya virus and Yellow Fever virus. See our website for more details: http://www.vignuzzilab.eu.

Keywords: quasispecies, polymerase fidelity, RNA virus, virus evolution

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  Publications

1: Vignuzzi M, Wendt E, Andino R. 2008. Engineering attenuated virus vaccines by controlling replication fidelity. Nat Med. 2008 Feb;14(2):154-61. PMID: 18246077

2: Geller R, Vignuzzi M, Andino R, Frydman J. 2007. Evolutionary constraints on chaperone-mediated folding provide an antiviral approach refractory to development of drug resistance. Genes Dev.2007 Jan 15;21(2):195-205. PMID: 17234885

3: Vignuzzi M, Stone JK, Arnold JJ, Cameron CE, Andino R. 2006. Quasispecies diversity determines pathogenesis through cooperative interactions in a viral population. Nature. 2006 Jan 19;439(7074):344-8. Epub 2005 Dec 4. PMID: 16327776



  Web Site

More informations on our web site




Activity Reports 2009 - Institut Pasteur
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