Author Description

Baculoviruses are enveloped, double-stranded DNA viruses that are pathogenic predominantly to insects. Insects, such as caterpillars, become infected by oral feeding on proteinaceous occlusion bodies (OBs) containing the occlusion-derived virus (ODV) form of the virus. The ODV infects epithelial cells in the midgut of the host insect. In infected cells, a budded virus (BV) form of the virus is first produced, which is then responsible for the systemic infection of the host. The BV entry into target insect cells is mediated by envelope fusion proteins that are present on the surface of BVs upon low pH activation. In this thesis the structure and activation mechanism of the baculovirus envelope fusion protein F were studied. The low-pH triggered, postfusion structure of soluble baculovirus F protein revealed remarkable resemblance with mammalian RNA virus respiratory syncytial virus (RSV). Furthermore, an F homolog of mosquito Anopheles darlingi (Ad-F) was shown to share structural features and amino acid homology with the baculovirus F protein and appears to have fusion function. It was further found that histidines may involved in low pH sensing to trigger conformational changes of baculovirus F protein, yet the highly conserved histidine residues are not pH sensors but some of them may participate in fusion pore expansion. Moreover, the baculovirus BV morphology was reanalyzed using cryo-electron microscopy to main the native virus structure. The study emphasized on several new features of BV structure including ovoid-shaped virion with polar distributed envelope (fusion) proteins and the empty lateral space between the nucleocapsid and envelope of the BVs. This thesis provides novel structural details of the low-pH triggered baculovirus F protein in relation to its fusion mechanism. The gained structural knowledge sheds new light on the evolutionary relationship of the baculovirus F proteins with homologs found in mammalian viruses and insects.