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

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

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

4. 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.

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

6. 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.

7. 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.

8. Virion
Papillomaviruses cause warts and other skin and mucosal lesions

9. 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

10. Genome
The infectious cycle follows differentiation of epithelial cells

11. 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 Genetic and transcriptional map of human papillomaviruses.

12. Genes and proteins

13. Genes and proteins
Common pathways used by viral oncogenes

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

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

16. 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

17. Vaccines

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