Papillomaviruses Papillomaviridae

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PapillomavirusesPapillomaviridae
Virion
Genome
Genes and proteins
Viruses and hosts
Diseases
Distinctive characteristics
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PapillomavirusesPapillomaviridae

• Virion
• Naked icosahedral capsid (T7).
• Diameter 55 nm.
• Formed from 72 capsomers, pentamers of L1.

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PapillomavirusesPapillomaviridae

• Genome
• Circular ds DNA, 8 Kb.
• DNA is packaged as minichromosome with cellular
  nucleosomal histones.

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PapillomavirusesPapillomaviridae

• 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.

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PapillomavirusesPapillomaviridae

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

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PapillomavirusesPapillomaviridae

• 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.

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PapillomavirusesPapillomaviridae

• 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.

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Virion

• Papillomaviruses cause warts and other skin and
  mucosal lesions

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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

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Genome

• The infectious cycle follows differentiation of
  epithelial cells

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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.
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Genes and proteins
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Genes and proteins

• Common pathways used by viral oncogenes

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Genes and proteins

• Viral E7 protein interacts with cell cycle
  regulatory proteins, particularly Rb

Fig. 11.5 Papillomavirus E7 protein activates
cell cycle progression.
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Genes and proteins

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

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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

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Vaccines
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Key Terms

• Apoptosis
• Basal cells
• Condyloma
• Keratinocytes
• Mucosal epithelium
• Pap test
• Proteasome

• Raft culture
• Retinoblastoma (Rb)
• Squamous cell carcinoma
• Tumor suppressor protein
• Ubiquitin
• Ubiquitination