Infection with Human Papillomavirus alters expression of the small proline rich proteins 2 and 3.
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.
Lehr
Elizabeth
E
Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
Hohl
Daniel
D
Huber
Marcel
M
Brown
Darron
D
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
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