WP5 - Role of interferon (IFN) in the pathogenesis of avian influenza viruses

Partners involved:
N° 3, Prof. Kristien Van Reeth (WP Leader)
N° 4, Dr. Mikhail Matrosovich

WP5 will investigate the pathogenesis of influenza virus in a natural virus host, the pig. The pig model of influenza virus infection is of great relevance for veterinary and human medicine. There are remarkable similarities between swine and humans regarding the pathogenesis of influenza and the immune response to influenza, in addition to respiratory and metabolic similarities between swine and humans. WP5 will determine the beneficial or detrimental effects of IFN in the pathogenesis of influenza in swine. More specifically, it will determine whether differences in the susceptibility of pigs to different avian influenza viruses and/or in the virulence of avian viruses for pigs may be due to differences in the IFN response. Pigs are highly susceptible to influenza viruses that are antigenically related to human influenza viruses. Therefore, we will first study which beneficial or harmful effects of an infection of pigs with swine influenza virus are mediated by IFNs. Second, we want to get insights into the parts/proteins of the influenza virus that are responsible for IFN induction in cells of the host. Third, we will examine whether different avian influenza viruses may show intrinsic differences in mammalian cells with respect to induction of IFN or susceptibility to the antiviral effects of IFN. Finally, we will study the exact role of IFN during an infection of pigs with avian influenza viruses. We will use AI viruses with differences in their IFN response, if possible, as well as neutralizing anti-IFN antibodies.