B. MAZEL-SANCHEZ¹, I. CARVALHO¹, M. SCHMOLKE<sup>1

1</sup>Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland

Influenza A viruses (IAV) are the etiological agent causing a common respiratory infection, influenza. PB1-F2 was identified an important pathogenicity factor. However, this small protein does not contain any intrinsic enzymatic activity and thus likely requires host proteins to mediate its phenotype. We identified a number of host interactors of PB1-F2 under infection conditions using highly sensitive LC-MS/MS. Here we decided to focus on the mitochondrial factor HCLS1-associated protein-X (HAX-1) in more detail. HAX-1 is ubiquitously expressed and was initially described as an anti-apoptotic factor, albeit this largely depends on the investigated cell type. We hypothesized that HAX-1 might play a role in the pathogenicity induced by PB1-F2. First, we confirmed the interaction of HAX-1 and PB1-F2 by IP-WB and confocal IF. Next, we generated cell lines overexpressing or knock-out for HAX-1 and analysed virus replication. HAX-1 overexpression inhibits viral replication of a virus lacking PB1-F2. This dependence on PB1-F2 to overcome HAX-1 restriction appears to be specific for avian viruses but is alternatively compensated in human isolates. Thus, human HAX-1 might be a specific inhibitor of avian influenza A viruses in humans. We are now investigating the functional mechanism by which HAX-1 inhibits avian isolates but not human ones on a molecular level.