Please use this identifier to cite or link to this item: https://knowledgecommons.lakeheadu.ca/handle/2453/388
Title: The life cycle of human papillomavirus type 16 E6 variants and its effects on the innate immune system of host keratinocytes
Authors: Jackson, Robert
Keywords: Human papillomavirus;Host keratinocytes;Host cells;Host immune response;Host cell transformation;HPV16
Issue Date: 1-Feb-2013
Abstract: Persistent infection with human papillomavirus type 16 (HPV16) is the primary aetiological agent for cervical cancer. Viral particles initiate their life cycle by infecting basal keratinocytes of epithelium and amplifying their genome. Viral oncoproteins E6 and E7 are responsible for causing host cells to proliferate, disrupting the regular differentiation regimen. Infections are typically cleared by a host immune response, but HPV16 is capable of persisting, increasing the chance of genomic integration and host cell transformation. It is thought that HPV16 can evade the innate immune response by down-regulating important molecules such as toll-like-receptors (TLRs): normally responsible for recognizing viral infection and activating immune-response genes by a signal transduction cascade. Epidemiological studies show natural E6 variants, Asian-American (AA) and L83V, are found more often than the prototype in invasive cervical cancers. Increased oncogenic potential for AA and L83V E6 genes has been confirmed by recent studies, but the role of the viral life cycle remains uncertain for each variant. The effects of an active viral life cycle on innate immunity were tested by first establishing an organotypic tissue culture model for mimicking HPV-infected epithelium. This model was phenotypically verified by morphology and immunohistochemistry for HPV16 L2 capsid protein, proliferation marker BrdU, and differentiation markers K5 and K10. Expression analysis for viral and innate immune genes was performed using RT-qPCR. Significantly, TLR3 and IFN-κ were down-regulated in AA and L83V variants compared to prototype HPV16, indicating a variant-specific viral life cycle effect on host innate immune defence. Future high-throughput analyses, such as microarray or RNA-sequencing, can be used for global expression profiling.
URI: http://knowledgecommons.lakeheadu.ca/handle/2453/388
metadata.etd.degree.discipline: Biology
metadata.etd.degree.name: Master of Science
metadata.etd.degree.level: Master
metadata.dc.contributor.advisor: Zehbe, Ingeborg
metadata.dc.contributor.committeemember: Malek, Ladislav
Qin, Wensheng
Appears in Collections:Electronic Theses and Dissertations from 2009

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