Human Papillomaviruses Infection
Department of Pathophysiology of Mucocutaneous Disorders, Graduate School of Medicine, Nippon Medical School
Human papillomaviruses (HPVs) represent a family of diverse DNA viruses consisting of more than 100 types and have been extensively studied as an etiological factor in benign and malignant tumors. In malignant epithelial lesions, the mechanism by which two E6 and E7 proteins of the high risk HPV types, HPV 16 and 18 interact with cellular factors in deregulating the normal growth of the cells, has been well described by many authors. The E6 and E7 proteins are consistently expressed in HPV-associated malignant tumor and E6 binding to the p53 gene mediated by the E6-associated protein ligase turned out to be important. In contrast important function of E7 was demonstrated by its binding to pRb and Rb-related proteins. The bindings under phosphorylation of these proteins was degradated by ubiquination and transcription factors of the E2F regulated cell proliferation. Overall HPV 16 DNA is able to induced modifications in the host cells and immortalizing epithelial cells by stimulating human telomerase reverse transcriptase (hTERT) protein. High risk E6 proteins directly interacts with c-myc and c-myc/E6 complex activates hTERT protein expression.
The various methods for detection or cloning of HPV DNA are summarized in this manuscript. PCR method has been become an established technique for detecting a large number of HPV DNAs. In particular PCR-RFLP is a simple and useful method for identifying the specific HPV types. However many modifications of the methods have been developed. Recently clinical trials are being conducted to test the preventive efficacy of HPV vaccines, directed against HPV 16 and 18 in Japan. In the future the therapeutic efficacy of HPV vaccines are required to prevent cervical cancer and other HPV associated cutaneous carcinomas.
ϊγεγο 2007; 3(4), 170-178
human papillomaviruses, E6, E7, telomerase, cloning, therapy
Tsuyoshi Mitsuishi, Department of Dermatology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan