Location: Foreign Animal Disease Research
Project Number: 1940-32000-056-07
Start Date: Aug 01, 2010
End Date: Mar 31, 2014
To fulfill objective 1, a set of genetically modified full-length cDNA copies of CSFV and a set of ASFV deletion mutants will be constructed from parental virulent viruses. Virulence of mutant viruses will be determined in swine relative to virulence of parental viruses. We expect that introduced changes will render viruses phenotypically different from virulent parental viruses. Relevant cellular signaling pathways altered by CSFV and ASFV infections will be revealed by further characterizing recombinant and parental viruses cycles in susceptible swine cells (i.e. primary swine macrophage cultures). The expression of relevant immunomodulatory genes will be assessed by qPCR. Identification of host cellular proteins interacting with viral proteins involved with virus virulence will be identified by means of the yeast two hybrid system. Colocalization of expressed virus proteins and interacting host proteins within infected macrophages will be performed by confocal microscopy. To fulfill objective 2, infections with wild-type and highly attenuated mutant CSFV and ASFV will be established in vivo and animals will be challenged with wild type viruses to assess the protective efficacy of recombinant viruses in exposed swine. Identification and characterization of host and viral proteins mediating disease will be an important goal in this project. Overall experimental manipulation of identified host-virus interactions may be used for developing novel tools for controlling virus infection in vivo.