VIRMUT

Variability in the mutation rate of RNA viruses

Coordinatore	UNIVERSITAT DE VALENCIA    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	Spain [ES]
Totale costo	1˙432˙021 €
EC contributo	1˙432˙021 €
Programma	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)
Code Call	ERC-2011-StG_20101109
Funding Scheme	ERC-SG
Anno di inizio	2012
Periodo (anno-mese-giorno)	2012-01-01   -   2016-12-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE  Organization address address: Rue Michel -Ange 3 city: PARIS postcode: 75794 contact info Titolo: Dr. Nome: Christine Cognome: Brunel Email: send email Telefono: 33388106050	FR (PARIS)	beneficiary	16˙200.00
2	UNIVERSIDAD DE CASTILLA - LA MANCHA  Organization address address: CALLE ALTAGRACIA 50 city: CIUDAD REAL postcode: 13071 contact info Titolo: Ms. Nome: Maria Llanos Cognome: Carrion-Varela Email: send email Telefono: +34 967 599 354 Fax: +34 967 599 305	ES (CIUDAD REAL)	beneficiary	16˙200.00
3	UNIVERSITAT DE VALENCIA  Organization address address: AVENIDA BLASCO IBANEZ 13 city: VALENCIA postcode: 46010 contact info Titolo: Dr. Nome: Rafael Cognome: Sanjuán Verdeguer Email: send email Telefono: 34963543270 Fax: +34 963 54 3670	ES (VALENCIA)	hostInstitution	1˙399˙621.00
4	UNIVERSITAT DE VALENCIA  Organization address address: AVENIDA BLASCO IBANEZ 13 city: VALENCIA postcode: 46010 contact info Titolo: Ms. Nome: Angeles Cognome: Sanchis Email: send email Telefono: +34 96 3983621 Fax: +34 96 3937729	ES (VALENCIA)	hostInstitution	1˙399˙621.00

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 Obiettivo del progetto (Objective)

'RNA viruses are the fastest evolving entities in nature. Such rapid evolution is explained by their mutation rates, which are orders of magnitude higher than those of DNA organisms. The error-prone replication of RNA viruses also has public-health implications related to pathogenesis, antiviral research, or viral emergence. However, current mutation rate estimates vary by more than 100-fold across different RNA viruses and sometimes over one order of magnitude for the same virus, and the causes of this variation remain poorly understood. Here, we plan to investigate variability in the mutation rate of RNA viruses at different levels. First, polymorphic sites in viral polymerases could produce populations with heterogeneous mutation rates, and the spread of genotypes with altered mutation rates might influence viral fitness and disease progression. Second, spontaneous mutations might occur preferentially at some regions of the viral genome, and these mutational hotspots could match genome regions where the selective pressure imposed by the host is strongest, thereby increasing viral adaptability. Third, RNA viruses with different types of genomes, such as single-stranded versus double-stranded RNA or sense versus anti-sense genome polarity might differ in their susceptibility to nucleic-acid damage or host-mediated editing and thus, in their mutation rate. Fourth, RNA viruses with larger genomes might have evolved increased replication fidelity to compensate for their greater genetic load. To address these issues, we will use several biomedically relevant and/or model viruses, including HIV-1, hepatitis C virus, a rotavirus, a coronavirus and a bacteriophage. The experimental procedures will include in vitro replication fidelity assays, ex vivo infections using cell cultures, and analysis of patient samples by next-generation sequencing. This thorough and multilevel approach may reveal previously unrecognized mechanisms for generating diversity in RNA viruses.'