The baculovirus per os infectivity complex

Insect larvae are orally infected by baculoviruses through ingestion of proteinaceous occlusion bodies (OB) containing the so-called occlusion derived viruses (ODV). OBs disintegrate in the alkaline environment of the insect midgut releasing the ODV, which then bind and fuse with the microvillar membrane of epithelial cells thereby initiating infection. After replication and spread through the larval body, ODVs are assembled and occluded into OBs. In this thesis the protein structure of ODVs and their entry into microvillar cells were studied from the perspective of protein-protein interactions. A number a novel interactions were identified among ODV structural proteins shedding light on the spatial and temporal mechanism of ODV assembly. Furthermore, a group of highly conserved viral per os infectivity factors (PIF) was shown to form a complex on the ODV envelope. These PIF proteins are essential for oral infectivity of ODVs and the complex may play a pivotal role in binding and fusion of ODV with the microvillar membrane. It was further found that in the OB structure a host derived alkaline protease was tightly associated with ODVs and cleaved one of the PIF proteins (P74). Proteolytic processing of PIF proteins may be necessary to trigger conformational changes in the complex to facilitate its function in binding and fusion with the host cell membrane. This thesis provided not only novel insights on the mechanism of ODV entry and assembly and the role of individual ODV proteins, but also triggered new questions to direct future investigations.