title: Infection with Human Papillomavirus alters expression of the small proline rich proteins 2 and 3.
abstract: Human papillomavirus (HPV) does not induce lysis of infected keratinocytes, and the exact mechanisms of viral escape are not known. As keratinocytes differentiate, the cornified cell envelope (CCE) develops, providing a protective barrier to the host. Our prior studies have identified abnormalities in CCEs isolated from genital epithelium infected with HPV 11 (a low-risk HPV type) and HPV 59 (a high-risk HPV type). These abnormalities included reduced thickness and increased fragility compared to CCEs in healthy epithelium. Transcription of loricrin is also reduced in HPV 11- and 59-infected epithelium. In this study, uninfected and HPV 11- or 59-infected human genital epithelium were examined for expression of the small proline rich proteins (SPRs), which serve as cross-linking proteins within the CCE. Limiting cycle RT-PCR was performed to detect the various SPR transcripts in HPV 11- and 59-infected, or uninfected epithelium. Immunohistochemical analysis and immunoblot assays were performed to analyze the distribution and quantity of SPR2A, SPR2B, and SPR3. SPR2B transcripts were moderately increased in the HPV 11- and 59-infected tissues and SPR3 transcripts were significantly increased in HPV 11-infected tissues and minimally increased in HPV 59-infected tissues. SPR2B protein quantities were moderately increased while SPR2A was not significantly changed. SPR3 protein, while not present in uninfected epithelium, was detected in abundance in HPV 11-infected tissue. We conclude that low-risk and high-risk HPVs share the ability to alter expression of CCE proteins, although the exact mechanisms may differ. Expression of individual SPRs differed between these types and these alterations may play a role in fragility of CCEs in HPV infection.
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Lehr
authors.forename: Daniel
authors.initials: D
authors.lastname: Hohl
authors.forename: Marcel
authors.initials: M
authors.lastname: Huber
authors.forename: Darron
authors.initials: D
authors.lastname: Brown
mesh_terms: D000818:Animals; D055233:Cornified Envelope Proline-Rich Proteins; D004847:Epithelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D015151:Immunoblotting; D007381:Intermediate Filament Proteins / Q000096:biosynthesis* / Q000235:genetics; D015603:Keratinocytes / Q000378:metabolism / Q000821:virology; D051379:Mice; D008819:Mice, Nude; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000378:metabolism* / Q000821:virology; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016038:Skin Transplantation; D014183:Transplantation, Heterologous
chemical_list: D055233:Cornified Envelope Proline-Rich Proteins; D007381:Intermediate Filament Proteins; D011506:Proteins; D012333:RNA, Messenger; C491986:SPRR2B protein, human; C491987:SPRR2D protein, human; C112254:SPRR3 protein, human