Infection with the oncogenic human papillomavirus type 59 alters protein components of the cornified cell envelope.
Infection of the genital tract with human papillomaviruses (HPVs) leads to proliferative and dysplastic epithelial lesions. The mechanisms used by the virus to escape the infected keratinocyte are not well understood. Infection of keratinocytes with HPV does not cause lysis, the mechanism used by many viruses to release newly formed virions. For HPV 11, a type associated with a low risk of neoplastic disease, the cornified cell envelope (CCE) of infected keratinocytes is thin and fragile, and transcription of loricrin, the major CCE protein, is reduced. The effects of high-risk HPV infection on components of the CCE have not been previously reported. HPV 59, an oncogenic genital type related to HPV types 18 and 45 was identified in a condylomata acuminata lesion. An extract of this lesion was used to infect human foreskin fragments, which were grown in athymic mice as xenografts. Continued propagation using extracts of xenografts permitted growth of additional HPV 59-infected xenografts. CCEs purified from HPV 59-infected xenografts displayed subtle morphologic abnormalities compared to those derived from uninfected xenografts. HPV 59-infected xenografts revealed dysplastic-appearing cells with mitotic figures. Detection of loricrin, involucrin, and cytokeratin 10 was reduced in HPV 59-infected epithelium, while small proline-rich protein 3 (SPR3) was increased. Reduction in loricrin was most apparent in regions of epithelium containing abundant HPV 59 DNA. Compared to uninfected epithelium, loricrin transcription was decreased in HPV 59-infected epithelium. We conclude that HPV 59 shares with HPV 11 the ability to alter CCE components and to specifically reduce transcription of the loricrin gene. Because loricrin is the major CCE protein, a reduction in this component could alter the physical properties of the CCE, thus facilitating virion release.
Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Elizabeth
E
Lehr
Darron R
DR
Brown
D001483:Base Sequence; D017931:DNA Primers; D004847:Epithelial Cells / Q000473:pathology / Q000821:virology; D006801:Humans; D017403:In Situ Hybridization; D008565:Membrane Proteins / Q000235:genetics; D027383:Papillomaviridae / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D030361:Papillomavirus Infections / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014412:Tumor Virus Infections / Q000473:pathology*; D014759:Viral Envelope Proteins / Q000378:metabolism*
D017931:DNA Primers; D008565:Membrane Proteins; D014759:Viral Envelope Proteins; C064554:loricrin