Grant: Discovery Grants Program - Individual

The Nyaviridae are a recently identified, new virus family for which only limited knowledge concerning their biology and their pathogenic potential is available. The proteins of the Nyaviridae share only minimal similarity with proteins of closely related viruses indicating that the Nyaviridae proteins represent novel structural solutions for common viral tasks like cell entry, genome amplification and virus assembly. To gain more insight into the biology of the Nyaviridae we established experimental systems for the characterization of viral protein function. Our analyses demonstrated an unexpected arrangement of protein functions and identified an atypical organization of the viral genome. We further found that the Nyaviridae replicate in the nucleus rather than in the cytoplasma as most other closely related viruses do. To analyze the consequences of nuclear replication for genome amplification and particle formation in more detail and to identify protein functions affecting the pathogenic potential of the Nyaviridae, we propose a research program with two objectives: 1) To characterize protein interactions regulating viral replication and assembly. We will use genetically modified viruses expressing viral proteins that can be traced by fluorescent microscopy in infected cells. 2) To identify the proteins responsible for the inhibition of cellular defense mechanisms. We expect that our studies provide novel insights into the structure-function relationship of viral proteins and will increase our understanding of mechanisms that govern replication and assembly processes in viruses with a nuclear replication phase.