During the infection of a cell, a virus gets in contact with many host proteins. These interactions between virus and host factors enable the virus the successful production of progeny and progress of the disease. Identification and characterization of such interactions could be useful in providing novel alternatives to alter virus multiplication and, perhaps, disease. This project proposed the identification of swine proteins interacting with classical swine fever virus (CSFV) proteins during the infection. Results obtained enable the identification of several host proteins interacting with CSFV structural protein Core. Core protein is the major contributor to the virus capsid. Several of these interactions have been studied in detail and the regions of the CSFV Core protein interacting with the host proteins were identified. Mutant CSFV viruses having altered these regions have been demonstrated that have severely altered their ability to produce disease in swine. Therefore, the manipulation of the identified host-virus interactions allowed the development of attenuated strains of virus which may constitute a tool for the further development of live attenuated vaccine against classical swine fever. Additionally, this knowledge may open the possibility of designing bio therapeutic compounds that could alter those critical interactions that may limit the spread of the disease.