Human Pailloma and Polyoma Viruses

Question 1

Papillomaviruses Structure

Answer 1

• ds DNA circular
• icosohedral, naked
• Genomic diversity among papillomaviruses
• More than 100 genotypes of human papillomaviruses (HPVs) have been identified
• Viral components can be detected in infected cells

Question 2

Papillomaviruses encode [] and [] proteins.

Answer 2

Papillomaviruses encode early (E1-E8) and late (L1-L2) proteins.

Question 3

[] proteins are required for replication and [] proteins form the structure of the virus.

Answer 3

Early proteins are required for replication and late proteins form the structure of the virus.

Question 4

Papillomavirus Replication

Answer 4

• Entry (viropexis) ——>Transcription (host RNA polymerase)——>Early viral protein synthesis (E1-E8)——>DNA replication (host DNA polymerase)——>Late viral protein synthesis (L1, L2)——>virus assembly in the nucleus——>virus release by cell destruction
• Close contact allows virus entry
• Early transcription/replication in lower portion of epidermis
• Vegetative DNA (genome) replication occurs in more differentiated cells of epidermis
• No cellular DNA synthesis
• Burst of viral DNA synthesis to generate viral genomes for packaging of progeny viruses

Question 5

Papillomavirus Transmission

Answer 5

• Public showers/swimming pool suspected
• Occupational exposure
• Meat and fish handlers are prone to hand warts
• Sexually (20 to 60% females in the U.S. are infected)
• Genital warts ~65% of sexual contacts develop an infection
• Perinatally

Question 6

Papillomavirus Incubation

Answer 6

•1-8 months (average 3 months)

Question 7

Papilloma Virus Infection - Type 6 and 11

Answer 7

• low risk
• cause most common (about 90%) benign genital warts in males and females with some cellular dysplasia of the cervical epithelium, rarely becomes malignant.

-External genital HPV infection occurs as exophytic genital warts (condylomata acuminata)

• Can be transmitted through oral sex (7% of teens and adult carry oral HPV, risk of mouth and throat cancer)
• HPV types 6 and 11 have been associated with nasal, oral, conjunctival, and laryngeal warts, although high-risk genotypes (type 16 and 18) are associated with oropharyngeal cancer
• Can be perinatally transmitted from mother-to-child and cause infantile laryngeal papillomas

Question 8

Papillomavirus Infection - Types 16,18,31,33,45,52,58

Answer 8

• high risk
• may cause lesions of the vulva, cervix, and penis
• Several others types have also been implicated such as 35, 39, 56, 59, 66, and 68 in dysplasia and carcinoma.
• Development of cervical cancer and its precursor lesion, cervical intraepithelial neoplasia (CIN)
• Infections with these viral types, especially type 16 and 18, may progress to malignancy
• HPV-16 is probably the most carcinogenic genotype because of its association with 60% of cervical cancers, whereas HPV-18 association is about 10-15% 
• HPV is the major cause of most carcinomas of the cervix

Question 9

Papillomavirus Pathogenesis

Answer 9

• First DNA viruses linked to malignancy
• HPV genome can be detected in the nuclei of both benign and malignant tumors
• Mechanism of oncogenicity not understood

Question 10

Which viral genes are involved in transformation?

Answer 10

E7, E6 and E5 of higher HPV genotypes

Question 11

E7 interacts with [] to abrogate cell cycle regulation mediated by [].

Answer 11

E7 interacts with pRB to abrogate cell cycle regulation mediated by pRB.

Question 12

E6 accelerate the degradation of [] and reduces stability.

Answer 12

E6 accelerate the degradation of p53 and reduces stability.

Question 13

E5 more functional in [].

Answer 13

E5 more functional in benign papillomas.

Question 14

DOes the viral genome integrate into cellular genome in tumors?

Answer 14

Viral genome exists as multiple copies and does not integrate into cellular genome in benign tumors but may integrate in malignant tumors.

Question 15

How does the host cell try and prevent tumor formation?

Answer 15

• Host cell produces a protein that inhibits the HPV transforming genes expression
• But this can be inactivated by products of the virus allowing malignant transformation

Question 16

Papillomavirus Diagnosis

Answer 16

• Papillomavirus infection leads to perinuclear cytoplasmic vacuolization and nuclear enlargement “koilocytosis” in epithelial cells of the cervix or vagina.
• These changes can be seen in a routine pap smear.
• Immunoassays to detect viral antigen
• In situ hybridization
• PCR to detect specific viral DNA

Question 17

Papillomavirus Treatment

Answer 17

• cryotherapy
• LEEP
• topical cytotoxins
• recurrences are common
• systemic and local interferon therapy
• electrocautery
• radiation/chemo

Question 18

Papillomavirus Prevention

Answer 18

• Gardasil
• The vaccine is recommended for routine vaccination at age 11 or 12, females aged 13 to 26 years and males 13 to 21 not vaccinated previously and through age 26 for MSM and immunocompromised (HIV) not vaccinated before
• Not recommended during pregnancy
• Doses: Two: second shot 6-12 months after the 1st shot

Question 19

Polyomaviruses

Answer 19

• Polyomaviruses of the Polyomaviridae family
• ds DNA circular naked

Question 20

Polyomavirus Replication

Answer 20

Question 21

Polyomaviruses Epidemiology

Answer 21

• About 80% adults are seropositive
• Exact route of transmission unknown
• Respiratory or oral transmission (due to contaminated food or water) suspected

Question 22

Polyomaviruses Disease

Answer 22

• JCV: Progressive Multifocal Leukoencephalopathy (PML)
• BKV: Urinary tract infection, Hemorrhagic cystitis, Renal injury

Question 23

Progressive Multifocal Leukoencephalopathy (PML)

Answer 23

•Caused by JC virus

Rare, subacute, degenerative disease of the brain

• Primarily in adults with other chronic disease, especially AIDS
• Cerebrospinal fluid (CSF) findings are often normal, although some patients show a slight increase in lymphocytes and protein levels elevated
• Pathologically, foci of demyelination are found surrounded by giant, bizarre astrocytes containing intranuclear inclusions
• The demyelination is due to viral damage to oligodendroglial cells
• Characterized by the development of impaired memory, confusion and disorientation
• Followed by a multiplicity of neurologic symptoms
• Death could occur 3 to 6 months after onset of symptoms
• Incidence is on rise because of AIDS epidemic

Question 24

PML Diagnosis

Answer 24

• JCV particles can be seen by electron microscope
• JCV DNA sequences can be detected by PCR.

Question 25

PML Treatment

Answer 25

• No specific treatment for PML
• Reducing the immunosuppression may have some clinical benefit.

Question 26

BK Virus

Answer 26

• Infects large population
• Infection mainly latent
• BKV is associated with hemorrhagic cystitis, particularly in bone marrow and renal transplant recipients
• It also causes severe nephropathy and vasculopathy leading to kidney loss in renal transplant recipients
• May be reactivated to produce cystitis in immunocompromised patients
• Urinary Track Infection
• Found frequently in immunocompromised patients with JCV and BKV with no symptoms of renal injury
• BKV is associated with a hemorrhagic cystitis particularly in bone marrow and renal transplantation patients

Question 27

BK Virus Diagnosis

Answer 27

• Detection of cells in urine with BKV
• BKV can be cultured in vitro kidney cells
• Viral antigens can be detected in tissue by immunoassays