PublisherThe University of Arizona.
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AbstractThe early stages of Human Papillomavirus infection proceeds through a series of steps that involve interactions between cell surface molecules and viral capsid proteins. While the role of viral protein L1 in internalization of the virus has been well characterized, the role of minor capsid protein L2 in internalization and infection is less clear. However, cleavage of L2 by furin, a proprotein convertase, and the resulting exposure of an N-terminal region, the RG-1 epitope, has been shown to be a critical step in infection. In this study, we aimed to explicitly show furin cleavage during infection and identify the cellular conditions required for this cleavage event and establishment of infection. An assay to detect furin cleavage of L2 was developed, and for the first time, furin cleavage was directly shown during infection. In vivo data suggests that cyclophilin B, a peptidyl-prolyl isomerase believed to playa role in the conformational changes that occur prior to internalization, may playa less prominent role than previously thought. Understanding the role of L2 in entry and infection provides a more comprehensive picture of the mechanism of papillomavirus infection and exposure of the RG-1 epitope, the major target for next-generation broadly protective pan-HPV vaccines.
Degree ProgramHonors College
Biochemistry and Molecular Biophysics