Proteomic analysis reveals the actin cytoskeleton as cellular target for the human papillomavirus type 8

Recent studies strongly support a role of human papillomavirus type 8 (HPV8) in non-melanoma skin cancer development. In this study, a quantitative two-dimensional (2D) differential gene expression (DiGE) gel approach combined with mass spectrometry has been used to identify proteins that are abundantly deregulated in primary human epidermal keratinocytes expressing HPV8 sequences. Twenty six protein spots showed significant changes in the level of expression between keratinocytes expressing E7 or the complete early region (CER) of HPV8 compared to extracts from cells lacking HPV8 gene expression. No differences between HPV8 E7 alone and HPV8 CER expressing cells were observed. The 26 protein spots that were differentially expressed corresponded to 20 different proteins, of which 14 actin-associated proteins were downregulated except for calponin-2, which was the only actin-binding protein that was overexpressed. Besides changes in actin modulating proteins, an upregulation of cytokeratins (CK) 5, 6 and 14 was also noted. This study suggests that the actin and keratin cytoskeleton modulating proteins are targets for HPV8.