Analysis of novel functions and interaction partners of the influenza A virus PB1-F2 protein

• Applicant: Professor Dr. Stephan Ludwig
• Subject Area: Virology
• Term: from 2009 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 100021526

Influenza virus infections are still a major burden to human and animal health worldwide. Although these viruses have been extensively studied, the molecular basis of pathogenicity is still not fully understood yet. In 2001 a novel influenza virus protein with apoptosis promoting features, PB1-F2, has been identified. Recent work clearly demonstrated that the protein is an important pathogenicity factor in vivo, however the molecular basis of this function has not been elucidated yet. While functional studies on PB1-F2 so far were exclusively restricted to the proapoptotic features we were able to identify a completely novel role of the protein: PB1-F2 directly binds to the PB1 protein and thereby alters localization of the polymerase protein in the infected cell, leading to a small plaque phenotype of PB1-F2 knock-out viruses. In addition to this finding that will be further investigated in the project, we have identified novel cellular interaction partners in yeast two hybrid assays that suggest a role of PB1-F2 as an antagonist of the innate cellular defense. These completely new aspects of PB1-F2 biology will be further studied to elucidate the detailed molecular mechanisms and the relevance for viral pathogenicity.

• DFG Programme: Research Grants