Molecular mechanism involved in the pathogenesis of Classical swine fever

Abstract

Classical swine fever (CSF) is a fatal disease of pigs world wide which is endemic in India and classified as a notifiable disease by the World Organization for Animal Health. The genome of classical swine fever virus (CSFV), comprises four structural (C, Ems, El and E2) and eight non-structural (Npro, p7, NS2, NS3, NS4A, NS4B, NS5A and NS5B) proteins. Monocytes, in peripheral blood and macrophages in the various lymphoid organs, are its major targets. CSF disease is characterized by haemorrhagic fever and immunosuppression with generalized leukopenia including lymphopenia and granulocytopenia. CSFV Npro limits type I interferon induction in various cells by interacting with interferon regulatory factor 7. CSFV causes inhibition of nitric oxide production in infected macrophages and attenuation of nitric oxide bioavailability in vascular endothelial cells. CSFV infection produces enhanced reactive oxygen species production and induces oxidative stress. CSFV-infected pigs are largely affected by apoptosis in the thymus, spleen, lymph nodes, bone marrow and peripheral blood. Majority ofinfected cells were non apoptotic, but the apoptotic cells are primarily non-infected. CSFV NS2 protein inhibits cellular proliferation by the induction ofcell cycle arrest at S-phase which is beneficial for CSFV viral replication. After CSF infection in peripheral blood leukocytes 1745 genes showed altered expression. The proteins which show altered expression in PBMC after infection with CSFV includes cytoskeleton, protein translation and processing, heat-shock response, blood clotting and anti-oxidative stress proteins. Thestudy ofthese different molecular mechanisms involved in pathogenesis of CSFV may assist in the development of new antiviral therapies as well as innovative diagnostic methods.