Transgenic HPV11-E2 protein modulates URR activity in vivo

Area of Science:

• Molecular Biology
• Virology
• Genetics

Background:

• The E2 protein of human papillomaviruses (HPV) is known to bind the viral upstream regulatory region (URR) and modulate transcription.
• E2, along with E1, is essential for viral DNA replication.

Purpose of the Study:

• To develop a transgenic mouse model to study HPV URR function in vivo.
• To investigate the role of HPV11 E2 protein in regulating URR-driven gene expression within a living organism.

Main Methods:

• Generation of transgenic mice containing the HPV11 URR linked to a lacZ reporter gene.
• Generation of double transgenic mice co-expressing HPV11 E2 protein.
• Analysis of lacZ reporter gene expression in various tissues, focusing on hair follicles.

Main Results:

• Transgene expression driven by the HPV11 URR was exclusively detected in the bulge region of hair follicles in single transgenic mice.
• In double transgenic mice expressing HPV11 E2, reporter gene expression remained localized to hair follicle bulges.
• The presence of E2 significantly increased and broadened the statistical distribution of lacZ expression driven by the URR in hair follicles.
• HPV11 E2 demonstrated the capacity to both induce and repress URR activity in vivo.

Conclusions:

• The HPV11 URR directs gene expression specifically to the hair follicle bulge region in vivo.
• The HPV11 E2 protein plays a critical role in modulating the transcriptional activity of the HPV URR within the hair follicle environment.
• This transgenic model provides a valuable tool for studying HPV-host interactions and the function of viral regulatory elements in a physiological context.