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dc.contributor.authorFlores, Sonya Persia
dc.date.accessioned2012-08-27T20:44:08Z
dc.date.available2012-08-27T20:44:08Z
dc.date.issued2012-08-27
dc.date.submittedMay 2012
dc.identifier.urihttp://hdl.handle.net/1928/20978
dc.description.abstractHuman papillomaviruses (HPVs) are the causative agent of cervical cancer and infect skin and mucosal membranes. Through wounding the virus establishes infection in the basal layer of human keratinocytes and requires differentiating squamous epithelium to complete the viral life cycle. HPV virions contain two structural viral proteins: the major capsid protein L1 that self-assembles into capsid structures, and the minor capsid protein, L2, that is essential for infection. It is believed that HPV cellular entry occurs via receptor-mediated endocytosis and that the primary attachment factors used by the virus are heparan sulfonated proteoglycans (HSPGs). Most current HPV literature follows an entry model whereby L1 binds to HSPGs, causing a conformational change in the capsid, thus allowing access to a furin/proprotein convertase (PC) cleavage site on L2. Once L2 is furin-cleaved, the virus binds to a yet unknown secondary internalization receptor(s). There is, however, a body of experimental evidence that does not support this entry model. For example, L1-only virus like particles (VLPs) are able to enter cells with similar kinetics as L1/L2 VLPs and mutagenesis of the L2 furin cleavage site does not abrogate the virion’s ability to enter the cell. Furthermore, recent research in our laboratory indicates an alternative mechanism of HPV infection, whereby the virus binds to cell-anchored HSPGs that are normally in complex with a variety of ligands including growth factors (GF), cytokines, extracellular matrix (ECM) proteins, and proteinases. Ectodomain shedding of syndecan-1 and HSPG by matrix metalloproteinases (MMPs) allows the HPV-HSPG-GF complexes to become soluble and move to secondary GF receptors, thereby allowing the virus to gain access to the cell. While MMPs are known to activate many biological molecules, they themselves are activated by furin/PCs. Due to these new observations and the existence of experimental evidence that does not support the current model of HPV infection, we postulate that the function of furin has been misinterpreted. Our data suggest that a cellular component important for the infection process is also a target of furin/PC activity. Furthermore, we have found that multiple PC members play roles at different steps of HPV infection.en_US
dc.language.isoen_USen_US
dc.subjectHPVen_US
dc.subjectFurinen_US
dc.subject.lcshPapillomavirus diseases--Pathogenesis.
dc.subject.lcshProtein precursors.
dc.subject.lcshMetalloproteinases.
dc.titleThe role of furin in human papillomavirus infectionen_US
dc.typeThesisen_US
dc.description.degreeBiomedical Sciencesen_US
dc.description.levelMastersen_US
dc.description.departmentUniversity of New Mexico. Biomedical Sciences Graduate Programen_US
dc.description.advisorOzbun, Michelle
dc.description.committee-memberLidke, Diane
dc.description.committee-memberKajon, Adriana


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