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United States Department of Agriculture

Agricultural Research Service

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Research Project: EXPLOITING THE POTENTIAL OF LEADER PROTEINASE CODING SEQUENCE OF FOOT-AND-MOUTH DISEASE VIRUS TO DERIVE ATTENUATED STRAINS...COUNTERMEASURES

Location: Foreign Animal Disease Research

Project Number: 1940-32000-057-38
Project Type: Trust

Start Date: May 01, 2012
End Date: May 01, 2013

Objective:
The objective of this project is to improve recently developed novel strategies to control Foot-and-Mouth Disease (FMD). By mutating the leader protein (Lpro) coding region of the FMD virus, we were able to grow viruses which are less virulent than wild type viruses. This project will explore the incorporation of additional mutants in the Lpro region to decrease the probability of reversion to virulence and induce protective immune responses.

Approach:
1. Test the virulence in swine of FHA mutant FMDV. In vivo studies will be conducted in swine to test the virulence of an available mutant FMDV strain containing mutations in a conserved domain (FHA) of the virus leader coding region. 2. Construction and in vitro characterization of FMDV strains with mutations in the CTE domain and/or the SAP and/or FHA domains. Several mutant FMDV strains will be constructed by using the infectious clone and targeting conserved residues contained in the CTE region of the leader coding region with the goal of obtaining new stable attenuated phenotypes that have a low probability of reversion to virulent wild type phenotype. 3. Test the virulence in swine of FMDV strains containing multiple mutations in the leader coding region (SAP and/or FHA and/or CTE mutations). In vivo studies will be conducted in swine with newly constructed FMDV containing multiple attenuating mutations in the leader coding region. 4. Test the efficacy of vaccination with attenuated FMDV SAP mutant of serotype A against infection with wild type FMDV of different subtypes and serotypes. Heterologus subypes/serotype specific cross-protection will be assayed by vaccination of swine with FMDV SAP mutant of serotype A followed by challenging with wild type FMDV of serotype A24 or O and/or Asia. The role of induction of protective innate immunity such as the interferon response will be evaluated.

Last Modified: 7/28/2014
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