Characterisation of viral caspase inhibitors

Submission note: A thesis submitted in partial fulfilment of the degree of Masters of Science to the Department of Biochemistry, Latrobe Institute of Molecular Science, Faculty of Science, Technology and Engineering, La Trobe University, Bundoora.

Apoptosis is a process used to remove cells that are old, damaged and potentially dangerous. Infection of a host cell by a virus can trigger apoptosis, limiting virus production and spread. Many viruses have evolved strategies to delay or inhibit apoptosis by expressing proteins that target conserved members of the apoptotic pathway. The genome of a member of the baculovirus family was sequenced and it was proposed to encode a novel anti-apoptotic protein (choc15). Choc15 shows sequence homology to members of the P35 and P49 inhibitor families that have been shown previously to inhibit a range of caspases. This study tested the activity, specificity and quantitated inhibition of caspase activity by choc15 against a range of mammalian and insect caspases. BmP35 from Bombyx mori Nucleopolyhedrovirus previously showed an ability to inhibit caspase 3 activity in cell culture and cell free systems. BmP35 showed strong sequence homology to AcP35 but appears to have weaker inhibitory activity against caspases. This study also tested the activity, specificity and quantitated the inhibition by BmP35 against a range of caspases.