Intracellular expression patterns of the human papillomavirus type 59 E1/E4 protein in COS cells, keratinocytes, and genital epithelium.
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.
Brown
Darron R
DR
Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA. darbrow@iupui.edu
Brown
Calla R
CR
Lehr
Elizabeth E
EE
D000818:Animals; D019556:COS Cells; D002461:Cell Line, Transformed / Q000821:virology; D004848:Epithelium / Q000378:metabolism / Q000821:virology; D015870:Gene Expression; D005837:Genitalia, Male / Q000166:cytology; D006801:Humans; D015603:Keratinocytes / Q000201:enzymology / Q000378:metabolism / Q000821:virology; D008297:Male; D027383:Papillomaviridae / Q000235:genetics / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000378:metabolism*
D014759:Viral Envelope Proteins