Intracellular expression patterns of the human papillomavirus type 59 E1/E4 protein in COS cells, keratinocytes, and genital epithelium

Abstract

Objective: To compare and contrast the intracellular distribution pattern of the human papillomavirus type 59 (HPV 59) E1/E4 protein in COS cells, human keratinocytes, and naturally infected genital epithelium.

Methods: The HPV 59 E1/E4 protein was expressed in COS cells and NIKS cells (immortalized human keratinocytes). A subset of NIKS cells was induced to differentiate. The intracellular distribution pattern of E1/E4 and the effects of E1/E4 expression on the cytoskeleton network were compared for COS and NIKS cells. Expression of E1/E4 was examined in HPV 59-infected foreskin xenografts grown in athymic mice and in a natural HPV 59-infected genital lesion.

Results: The HPV 59 E1/E4 protein formed dense perinuclear inclusions in COS cells, similar to those reported for the HPV 16 E1/E4 protein. In contrast, the E1/E4 protein was diffusely cytoplasmic in undifferentiated NIKS cells, co-localizing with an intact cytokeratin filament network. The E1/E4 protein was concentrated in the region of the cornified cell envelope (CCE) of differentiated NIKS cells, co-localizing with involucrin, a CCE component. A similar distribution in the region of the CCE was observed for E1/E4 protein in HPV 59-infected human epithelial tissues.

Conclusions: The HPV 59 E1/E4 protein is cytoplasmic and co-localizes with an intact cytokeratin filament network in undifferentiated keratinocytes. The E1/E4 protein is distributed in the region of the CCE and co-localizes with involucrin in differentiated human keratinocytes, consistent with the intracellular distribution pattern observed in HPV 59-infected epithelium.