Download Introduction to Virology

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, doublestranded 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