Papillomaviruses Papillomaviridae Virion Genome Genes and proteins Viruses and hosts Diseases Distinctive characteristics

Papillomaviruses Papillomaviridae Virion Naked icosahedral capsid (T=7). Diameter 55 nm. Formed from 72 capsomers, pentamers of L1.

Papillomaviruses Papillomaviridae Genome Circular ds DNA, 8 Kb. DNA is packaged as “minichromosome” with cellular nucleosomal histones.

Papillomaviruses Papillomaviridae Genes and proteins Two transcriptional promoters and two polyadenylation signals (early and late) on same DNA strand. Splicing generates 10 or more different mRNAs. Early proteins E1 to E7 stimulate cell proliferation and enable viral DNA replication. Late proteins L1 and L2 form capsid.

Papillomaviruses Papillomaviridae Viruses and hosts Over 100 known human papillomaviruses. Other hosts: cattle, dogs, deer, rabbits, etc.

Papillomaviruses Papillomaviridae Diseases Benign warts at specific sites (skin, mucosa, larynx) depending on virus strain. Transmitted by direct contact. Some types cause cervical carcinoma, a sexually transmitted disease and major cause of cancer in women.

Papillomaviruses Papillomaviridae Distinctive characteristics Difficult to grow in vitro: require specialized raft cultures of epithelial cells. Replication pattern follows differentiation of epithelial cells in skin or mucosa. Early proteins E6 and E7 can transform cells in vitro, are expressed in cervical carcinomas.

Virion Papillomaviruses cause warts and other skin and mucosal lesions

Virion Oncogenic human papillomaviruses are a major cause of genital tract cancers HPV 16 ,18 – cervical cancer HPV 6, 11 – cervical warts Papillomaviruses are not easily grown in cell culture Papillomavirus genomes are circular, double-stranded DNA

Genome The infectious cycle follows differentiation of epithelial cells

Genome Viral mRNAs are made from two promoters and two polyadenylation signals Viral E1 and E2 proteins bind to the replication origin and direct initiation of DNA replication Fig. 11.2 Genetic and transcriptional map of human papillomaviruses.

Genes and proteins

Genes and proteins Common pathways used by viral oncogenes

Genes and proteins Viral E7 protein interacts with cell cycle regulatory proteins, particularly Rb Fig. 11.5 Papillomavirus E7 protein activates cell cycle progression.

Genes and proteins Viral E6 protein controls the level of cellular p53 protein Synergism between E6 and E7 and the predisposition to cancer

Genes and proteins Cells transformed by papillomaviruses express E6 and E7 gene products from integrated viral DNA Induce cellular DNA replication Prevent the cell from undergoing apotosis Future prospects for diagnosis and treatment of diseases caused by papillomaviruses Cervical smear test (Pap test) based on the recognition of morphologically abnormal cervical cells warts and precancerous tumors are removed by surgery or destroyed by liq N2 or laser

Vaccines

Key Terms Apoptosis Basal cells Condyloma Keratinocytes Mucosal epithelium Pap test Proteasome Raft culture Retinoblastoma (Rb) Squamous cell carcinoma Tumor suppressor protein Ubiquitin Ubiquitination