The biology of human papillomaviruses: from warts to cancer.
Papillomaviruses are small DNA viruses that induce a variety of proliferative lesions in most mammals, including humans. Of the 66 types of human papillomaviruses (HPVs) that have been identified, a subset that includes types 16, 18, 31, 33, and 51 is associated frequently with anogenital cancers. These cancers develop from precursor lesions, which, for cervical cancer, are termed cervical intraepithelial neoplasias (CIN), and are graded from I to III depending on the degree of disruption of epithelial differentiation. Viral production occurs in low-grade lesions that are only slightly alterated in their pattern of differentiation from normal cells. The production of viral particles, genome amplification, capsid protein synthesis, and virion assembly is dependent upon differentiation and is restricted to suprabasal cells. In carcinomas, viral DNA is usually found integrated into host chromosome, and no viral production is seen. The processes of viral transcription and replication are, therefore, intimately associated with the differentiation program of epithelial cells. In the past, studies on the life cycle of human papillomavirus have been limited due to an inability to faithfully duplicate the epithelial differentiation program in vitro. Recent advances in culture systems, have overcome these problems, allowing for the propagation of HPVs in vitro. In addition, insight has been gained at the molecular level regarding the mechanisms by which these viruses contribute to malignancy, centering on the action of the E6 and E7 viral oncoproteins. Evidence suggests that these oncoproteins function by inactivating the cell cycle regulators p53 and retinoblastoma, thus providing the initial event in a multistep progression to malignancy.
Laimins
L A
LA
Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, University of Chicago, Illinois 60637.
D001483:Base Sequence; D002472:Cell Transformation, Viral; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D015967:Gene Expression Regulation, Viral; D016679:Genome, Viral; D006801:Humans; D008969:Molecular Sequence Data; D027383:Papillomaviridae / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D030361:Papillomavirus Infections / Q000209:etiology*; D014412:Tumor Virus Infections / Q000209:etiology*; D014779:Virus Replication; D014860:Warts / Q000209:etiology*
D004279:DNA, Viral