Chapter 22

Papillomaviruses

Eukaryotic cells

Papillomavirus

Virion Structure

- Non-env icosahedral
- 55 nm in diameter
- T = 7 capsid Fig. 22.1 Papillomavirus virions.

Genome Structure
- circular dsDNA, 8 kb
- ~ 8 to 10 genes
- packaged as a “minichromosome” (cellular Histones)
- Replicated: cDdDp (nucleus) Transcribed: cDdRp

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 General Information

- over 100 known “types” infecting humans

- other hosts: e.g. cows, dogs, rabbits, etc.

- infect: mucosa or skin cells (i.e. epithelia)

- transmission: skin contact or contaminated surfaces

- diseases: benign warts or cancer (e.g. skin, cervical)

Fig. 22.3 Papillomavirus Infection of differentiating Epithelial Cells.

 Cell wart
division
& Nuclei Cell death
retained

dead
nucleus
Veg. Repl.
non-div. 1000’s

keratinocytes Late

(undiff.)
once/cell cyc
BECs
Early genes Initial repl: 50-100
HPV :binds Heparin & 6-Integrin  Endocytosis  Nucleus
(replicates)
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 Genome Structure: e.g. of type-16 & -31

Early (6): Repl. Late (2): Capsid

major
(8) minor
Ori
polyA signal = AAUAAA
Tc’n regl.

one E5, 6, 7 (cell proliferation)

BEC
strand E1, 2 (plasmid repl)
coding
E1, 2 (veg. repl)
Alternative Keratinocytes
splicing L1, L2
Fig. 22.2 Genetic and transcriptional map of human papillomaviruses.

Viral Gene Functions

e.g. of type-16 & -31

DNA genome replication by cDdDp in differentiated keratinocytes

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 A gene that contributes to A gene that contributes to
the induction of cancer the repression of cancer

Retinoblastoma (Rb)

Mutated in >50%
of human tumors

Fig. 22.4 Common pathways used by viral ONCOGENES.

Fig. 22.5 Papillomavirus E7 protein Activates cell cycle progression.

Rb protein: is a major regulator of the cell cycle
- binds to & represses E2F Tc’n factor
Unscheduled
DNA replication

can not bind to E2F

kinase
E2F activates cellular DNA synth.
free (G1  S )
cDdDp
For
virus 

E7 from oncogenic types

bind Rb more strongly
than non-oncogenic types
E7 can also direct
Ubiquitin-mediated degradation of Rb
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 Fig. 22.6 Interaction of papillomavirus E7 and E6 proteins with p53.
Virus-mediated unscheduled DNA
synthesis in
diff’ed cells
cellular ubiquitin
ligase

ubiquitinated

both CC ARREST &

APOPTOSIS are bad
for virus 
Only E6 from oncogenic
types mediate p53
degradation
Cell Cycle Happy
Progression virus 
Fig. 22.5

HPV Tumors: not planned by the virus

- p53 is not mutated in cervical cancers caused by HPV

- E6 & E7 become integrated into the cellular genome

- Expression results in “transformation” into a cancer cell

- No virus replication in transformed cells (HeLa cell line)

- HPV cancers most prevalent in developing countries

- HPV vaccines – VLPs – L1 (media: “cancer” vaccine)

Gardasil - FDA approval - June 2006 (both are prophylactic

Cervarix - “ “ - Oct. 2009 i.e. for prevention)

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 END of Chapter 22

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