Understanding the mechanism of influenza A virus PB1-F2 immune signalling antagonism

Avian influenza poses a major threat to animal health and food security. For instance, H5N1 influenza has been responsible for the deaths of over 300 million chickens since 2003. A better understanding of virus interactions with the avian host is therefore crucial to improve control strategies. This project will focus on the role of accessory proteins encoded by the virus genome. These proteins are non-essential for virus replication in vitro, but can modulate pathogenicity in vivo [1, 2]. PB1-F2 is a small accessory protein with a role in suppressing the inferferon response that is more highly conserved in avian than mammalian influenza isolates. We have recently shown that depending on virus strain, PB1-F2 can suppress innate immune signalling, decrease pathogenicity and lengthen viral shedding, extending the transmission window in chickens [2]. Our hypothesis is that influenza A virus PB1-F2 proteins have evolved to invoke suppression of innate signalling responses in avian hosts through variable mechanisms and that these differences partially explain pathogenicity. To interrogate this hypothesis the following questions will be studied;
1. What are the viral genetic determinants in PB1-F2 that influence the ability to antagonise the type I IFN or NF-kb (pro-inflammatory) signalling pathways?
What are the differences in the cellular interactome for PB1-F2 proteins that utilise these different mechanisms? How important are the prescribed functions of a PB1-F2 protein during infection of poultry within a defined viral genetic constellation?