EMERGENCE AND PATHOGENESIS OF SWINE INFLUENZA VIRUS: MICROEVOLUTION INFLUENCED BY IMMUNE RESPONSES

Influenza viruses are well known for engendering antigenic variations that consequently enable immune evasion. This viral characteristic is the bane of vaccine efforts against influenza, including in domestic swine production. During replication, the virus generates genome copies with poor fidelity. Host immune responses impose evolutionary pressure leading to the selection of mutant viruses with increased fitness. While studies on mice and human immune responses have shed some light on this process, little to nothing is known about the role of immune pressure on microevolution of swine influenza virus (SIV), which has continued to evolve in spite of vaccination. This gap in knowledge is in part due to the poor understanding of immune determinants on SIV. The present project will test the hypothesis that immune responses to SIV foster selective mutations on the viral genome, which in turn alters the pathogenic properties of emerging strains. The central hypothesis will be tested by addressing three specific aims: (1) To identify the major SIV determinants of porcine immune response (2) To define SIV mutations patterns derived under selective immune pressure (3) To evaluate microevolution of SIV isolates from vaccinated swine herds. This project also proposes developing an infectious agent repository to archive SIV samples that could be used in research of contemporary strains or for retrospective analysis of viral emergence. Given the concern that swine may serve as mixing vessels for the development of novel viruses and as intermediate hosts in interspecies transmission to humans, understanding mechanisms by which immune pressure directs antigenic variation in SIV is critical for developing effective vaccines.