Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Microbiology and Immunology

Supervisor(s)

Dr. Sung Kim

Abstract

Influenza virus type A (IVA) is the etiologic agent responsible for the febrile respiratory illness referred to as the flu. Seasonal and occasionally pandemic IVA-associated illness is a significant cause of morbidity and mortality worldwide, and presents a significant burden to the healthcare system. Our previous work showed that the propagation of IVA required the lysosomal protease cathepsin B (CTSB), though the mechanism behind this dependency was not elucidated. This study further examined the role of CTSB by using CTSB-deficient (CTSB-/-) macrophages and the CTSB-specific chemical inhibitor CA-074 Me (CaMe) in human lung epithelial cells. CTSB-/- and CA-074 Me-treated cells showed no defect in either the uptake of virus particles, nor their replication following endosomal escape compared to wildtype or non-treated cells, respectively. However, CTSB-/- and CA-074 Me-treated cells had significantly less hemagglutinin (HA) protein both inside and on the surface of infected cells, as determined by both Western blotting and confocal immunofluorescence microscopy. These results suggest that CTSB is required for a step(s) in the viral lifecycle following entry into host cells, either before or during the synthesis of viral proteins, and possibly during the transport of viral components to the host membrane. Further work is necessary to determine the mechanistic details of these observations, and may yield novel potential therapies for influenza infections.


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