Characterization of cricket paralysis virus-host interaction and viral protein synthesis

• Main Author: Khong, Anthony
• Language: English
• Published: University of British Columbia 2015
• Online Access: http://hdl.handle.net/2429/54692

Viruses are obligate parasites that have evolved strategies to recruit the translational machinery and inhibit antiviral defences. A relatively abundant family of positive-sense, monopartitate single stranded RNA viruses, dicistrovirus, remains relatively uncharacterized. Dicistroviruses are infectious to arthopods and have impacted a number of agricultural industries. Dicistroviruses, as indicated by their name, contain two open reading frames (ORFs). The 5'-untranslated internal ribosome entry site (5'-UTR IRES) directs translation of ORF1 which encodes non-structural proteins and the intergenic (IGR) IRES directs translation of ORF2 which encodes structural proteins. How dicistroviruses affect the host is not completely understood. My thesis focuses on several host pathways that are modulated during cricket paralysis virus (CrPV) infection, a model dicistrovirus. During CrPV infection, I discovered stress granule (SG) formation is inhibited but granules containing poly(A)+ mRNAs form. Furthermore, I discovered a viral protein, CrPV 1A, that inhibits the SG pathway. Upon further characterization of CrPV 1A, I discovered the viral protein also stimulates 5'-dependent translation and 5'IRES dependent translation. Finally, I found IGR IRES-dependent translation is delayed compared to 5'-UTR IRES-dependent translation, thus providing a viral strategy of expressing non-structural proteins such as the replicase and protease prior to the synthesis of structural proteins for viral packaging. This thesis provides insights into the key strategies of dicistrovirus infection, its viral life cycle and the innate immune responses in insect cells. === Medicine, Faculty of === Biochemistry and Molecular Biology, Department of === Graduate