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Content archived on 2024-06-18

The role of genetic diversity of RNA viruses in virulence and pathogenesis

Objective

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 (quasispecies) maintained by mutation-selection balance. RNA virus quasispecies have been observed for nearly all RNA viruses, but whether genetic heterogeneity is a function or consequence of a the virus’ interaction with its host environment has been difficult to answer, particularly in vivo. Recently, we have developed a model system to study these questions by altering the RdRp fidelity of poliovirus, thereby changing the amount of genetic diversity present in a population. We showed that viral infectivity, dissemination and pathogenicity were dependent on the level of genetic diversity present within a viral population. We also showed that restricting genetic diversity strongly attenuates virus and may constitute a novel strategy to engineer live virus vaccines. However, the poliovirus model of infection of transgenic mice presents significant differences and limitations with respects to a natural host infection. To further extend our preliminary results, we are shifting the expertise acquired in these recent studies to a more natural model of infection, using the Coxsackie B3 virus. This new model of study will permit a more detailed determination of the role of genetic diversity in pathogenesis and a more realistic evaluation of modulating genetic diversity as a vaccine approach.

Fields of science (EuroSciVoc)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

FP7-PEOPLE-IRG-2008
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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MC-IRG - International Re-integration Grants (IRG)

Coordinator

INSTITUT PASTEUR
EU contribution
€ 100 000,00
Address
RUE DU DOCTEUR ROUX 25-28
75724 Paris
France

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
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Total cost

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