Papovavirus family

(Papovaviridae) :

Papillomaviruses and
Polyomaviruses
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 PAPOVAVIRIDAE
• Name from: Papilloma Polyoma Vacuolating agent

• Suffix “oma” means swelling or tumor

• Two subfamilies: Papillomavirinae, Polyomavirinae

• Not very important as lethal human pathogens, but

cause warts and in some cases cancer
• The most common viral STD

• Highly restricted host ranges

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 Human papillomaviruses (HPVs):

• Warts
• human cancer (e.g., cervical and penile
carcinoma):
– several genotypes over 100 strains

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 Polyomaviridae

• BK and JC(John Cunningham) viruses,

 usually cause asymptomatic infections
 Cause disease only in immunosuppressed
people.
 Both are associated with cancer
– BK: renal disease
– JC: progressive multifocal leukoencephalopathy
(PML),
– Simian virus 40 (SV40), its link with some human
cancers e.g primary brain cancer and malignant
mesothelioma has been suggested but still debated
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 Polyomavirus Papillomavirus

•double-stranded •double-stranded
•circular DNA •circular DNA
Genom
e •~5kbp •~8kbp
•genome ~5000 •Genome ~ 8000 nucleotides
nucleotides  

•Noneveloped •Nonenveloped
Morpho
logy •~45 nm diameter •~52-55nm diameter
•icosohedral, skew, T= 7 •icosohedral, skew, T= 7
•3 capsid proteins •2 capsid proteins

Other
Differen •Subfamily specific antigens
ces •Papillomavirus can't be grown in culture, while polyomaviruses are often grown in culture

Most are asymptomatic,

Pathog Cause various types of warts, epidermodysplasia
although can be oncogenic in
enesis verruciformis
hamsters

Repres JC Virus
entative •Associated with Progressive multifocal
At least 62 strains of Human Papillomaviruses
Viruses leukoencephalopathy, found mainly in •Widespread
the elderly and immunocompromised
BK Virus •Cause growths or warts
•Results in mild respiratory illness in
kids •Many are associated with cancer
•Found in some tumors
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Simian Virus 40
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A completely sequenced animal virus used   5
frequently as a cloning vector.  
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 Unique Properties of Polyomaviruses and
Papillomaviruses

• Small, non-enveloped virus

• Double-stranded covalently closed circular DNA

genome
• Icosahedral symmetry

• Capsid proteins subunits VP1, VP2 and VP3. only VP1

Exposed on the surface of capsid.
• Viruses encode proteins that promote cell growth
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 Unique Properties of Polyomaviruses and Papillomaviruses

• These proteins bind to the cellular growth-suppressor

proteins p53 and p105RB (p105 retinoblastoma gene
product).
– Papilloma E6 binds to p53, and

– Papilloma E7 binds to p105RB

• lytic infections

• Persistent and latent infections

• immortalize (transform) cells

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 Human Papillomaviruses (HPV)

• Most important of papovavirus

• More than 100 distinct strains identified

• Cause common and genital warts, sometimes

associated with cancer.
• HPV can be distinguished further as cutaneous
HPV or mucosal HPV on the basis of the
susceptible tissue. Within the mucosal HPV,
there is a group associated
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 HPV

• infect and replicate in the squamous

epithelium of skin (warts) and

• mucous membranes (genital, oral, and

conjunctival papillomas) to induce
epithelial proliferation.

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 TRANSMISSION

• HPV resists inactivation

• can be transmitted on fomites, such as
the surfaces of countertops or furniture,
bathroom floors, and towels
• Asymptomatic shedding may promote
transmission.
HPV infection is acquired
(1) by direct contact through small breaks in the skin or mucosa
(2) during sexual intercourse
(3) while an infant is passing through an infected birth canal.

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 Disease Mechanisms of Papillomaviruses and
Polyomaviruses
Papillomaviruses

•Virus is acquired by close contact and infects the

epithelial cells of the skin or mucous membranes.
•Tissue tropism and disease presentation depend
on the papillomavirus type.
•Virus persists in the basal layer and then
produces virus in terminally differentiated
keratinocytes.
•Viruses cause benign outgrowth of cells into
warts.
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 Disease Mechanisms of Papillomaviruses and
Polyomaviruses
Papillomaviruses
•HPV infection is hidden from immune responses and
persists.
•Warts resolve spontaneously, possibly as a result of
immune response.
•Certain types are associated with dysplasia that may
become cancerous with the action of cofactors.
•DNA of specific HPV types is present (integrated) in the
tumor
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 Polyomaviruses (JC and BK Viruses)
• Virus is probably acquired through the
respiratory route and spread by viremia
to the kidneys early in life.
• Infections are asymptomatic.
• Virus establishes persistent and latent
infection in organs such as the kidneys
and lungs.
• In immunocompromised people,
– BK: Renal infection(nephropathy)
– JC virus is activated, spreads to the brain, and causes
progressive multifocal leukoencephalopathy (PML),
a conventional slow virus disease.

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 Epidemiology of Polyomaviruses and Papillomaviruses

Disease/Viral Factors
•Capsid virus is resistant to inactivation
•Virus persists in host
•Asymptomatic shedding is likely
Transmission
•Papillomavirus: direct contact, sexual contact
(sexually transmitted disease) for certain virus
types, or passage through infected birth canal for
laryngeal papillomas (types 6 and 11)
•Polyomavirus: inhalation or contact with
contaminated water
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 Epidemiology of Polyomaviruses and Papillomaviruses

Who Is at Risk?

•Papillomavirus: warts are common; sexually

active people are at risk for infection with
HPV types correlated with oral and genital
cancers
•Polyomavirus: ubiquitous;
immunocompromised people.
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 Human papillomavirus

• is possibly the most prevalent sexually transmitted

infection in the world,
• with certain HPV types common among sexually
active people.
• HPV is present in 99.7% of all cervical cancers.

• HPV-16, HPV-18, HPV-31, and HPV-45 are high-risk

• the second leading cause of cancer death in

women.
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 HPV

• 10% of women infected with the high-risk HPV

types will develop cervical dysplasia, a
precancerous state.

Major risk factors for infection and progression to

cancer:
– Multiple sexual partners

– smoking

– a family history of cervical cancer

– immunosuppression
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 HPV diseases

• Cutaneous Syndromes
• Skin warts  HPV1 through HPV4
• Mucosal Syndromes
• Benign head and neck tumors
• Laryngeal papilloma
• Oral papilloma
• Conjunctival papilloma
• Anogenital warts
• Condyloma acuminatum 6, 11
• Cervical intraepithelial neoplasia, cancer16, 18
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 Ssuuna Charles PG-MCB-MUST MLSO-
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© 2005 Elsevier
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© 2005 Elsevier
Papillomaviruses infect squamous epithelial cells and induce
within those cells a characteristic cytoplasmic vacuole.
These vacuolated cells, called koilocytes, are the hallmark of
infection by these viruses.
Most warts are benign and do not progress to malignancy.
The proteins encoded by viral genes E6 and E7 interfere with the
growth-inhibitory activity of the proteins encoded by the p53 and
RB tumor suppressor genes and thereby contribute to oncogenesis
by these viruses.

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 Laboratory Diagnosis of Papillomavirus Infections
• Pathology, cytology :PAP smear:Koilocytotic cells
• Immunohistochemistry
• Nucleic acid
– Hybridization (Southern, in situ), PCR
– Identification of specific HPV type can assist in
evaluating prognosis and treatment
Koilocytes
• characteristic of papillomavirus infection,
• are enlarged keratinocytes with clear holes around
shrunken nuclei

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 Papillomavirus cytology

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© 2005 Elsevier
 PREVENTION AND TREATMENT
Treatment
The usual treatment for genital warts is podophyllin;
alpha interferon is also effective and is better at
preventing recurrences
•Pap smear
•Surgery
Vaccine
– Tetravalent HPV vaccine (Gardasil) :HPV 6, 11, 16,
and 18; anogenital warts and cervical cancer.
– Bivalent HPV(Cervarix)(16,18)
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 Vaccine

A series of three immunizations is recommended

for girls ( boys), starting at age 11 prior to sexual
activity.
• The HPV vaccine is not a replacement for a PAP
smear, and women should continue to be tested.
• Proper precautions (e.g., the use of condoms) can
prevent the sexual transmission.
• The role of cesarean section is uncertain
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