Cel RNA viruses have the highest mutation frequencies in nature, which are in large part attributed to the low fidelity of their viral RNA-dependent RNA polymerases (RdRp). Explosive replication kinetics coupled with high mutation rates quickly generate highly diverse populations that have been observed for all RNA viruses. Recently, we have developed a model system to study the roles that RNA virus mutation rates and population heterogeneity play in virus fitness, virulence and pathogenesis in vivo. The system relies on altering the RdRp fidelity of poliovirus, thereby changing the amount of genetic diversity present in a population. We found that increasing or decreasing genetic diversity strongly attenuates the virus and may constitute a novel strategy to engineer live virus vaccines. However, the poliovirus infection model of transgenic mice presents significant limitations that do not permit more detailed studies of the mechanisms behind these observations. To further extend our preliminary results, we will develop two new infection models, to study the role of genetic diversity and population dynamics of RNA viruses infecting their hosts naturally. These models will be used to uncover the mechanisms by which genetic diversity is generated, the points in infection when it is critical and the specific bottlenecking events or subpopulations that are involved at these critical points. We will use new deep sequencing technology, coupled to concepts in population genetics, to develop new strategies for vaccine discovery based on the modulation of RNA virus populations. Dziedzina nauki natural sciencesbiological sciencesgeneticsmutationvirus mutation Słowa kluczowe RNA viruses mutation rates pathogenesis quasispecies vaccines Program(-y) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Temat(-y) ERC-SG-LS6 - ERC Starting Grant - Immunity and infection Zaproszenie do składania wniosków ERC-2009-StG Zobacz inne projekty w ramach tego zaproszenia System finansowania ERC-SG - ERC Starting Grant Instytucja przyjmująca INSTITUT PASTEUR Wkład UE € 1 870 000,00 Adres RUE DU DOCTEUR ROUX 25-28 75724 Paris Francja Zobacz na mapie Region Ile-de-France Ile-de-France Paris Rodzaj działalności Research Organisations Kontakt administracyjny Marie-Laure Rosso (Ms.) Kierownik naukowy Marco Vignuzzi (Dr.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych Beneficjenci (1) Sortuj alfabetycznie Sortuj według wkładu UE Rozwiń wszystko Zwiń wszystko INSTITUT PASTEUR Francja Wkład UE € 1 870 000,00 Adres RUE DU DOCTEUR ROUX 25-28 75724 Paris Zobacz na mapie Region Ile-de-France Ile-de-France Paris Rodzaj działalności Research Organisations Kontakt administracyjny Marie-Laure Rosso (Ms.) Kierownik naukowy Marco Vignuzzi (Dr.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych
