Other Medically Important DNA viruses

Question 1

Human Papilloma virus (HPV): diseases

Answer 1

o dsDNA, non-enveloped, icosahedral capsid

Two types of diseases:
!) Warts (types 6 & 11)
• Benign growths on skin and mucosal surfaces
• Can be flat macular, skin colored or red, or verrucous
Immune deficient = can develop Epidermodysplasia veruciformis
o Flat macular reddish spots
o Can convert of common squamous cell carcinoma in sun-exposed areas

2) Cancers (types 16 & 18)
• Anogenital intraepithelial neoplasias
• Laryngeal cancers (from infection of oropharyngeal mucosa)
• Bowen’s disease = cancerous lesions of labia

Question 2

Molluscum Contagiosum: diseases

Answer 2

o Parapox virus (related to smallpox)
o Only human poxvirus circulating naturally
o Transmitted by close contact
o Causes umbilicated papules on skin

o Immunocompetent = self-limited infection
o Immunocompromised = can spread and enlarge, mimic squamous cell carcinoma

Question 3

Parvovirus B19: diseases

Answer 3

o 50% people infected by age 15
o Seasonal: higher rates in late winter, spring, and early summer
o Usually asymptomatic or clinically mild

Diseases: 
Fifth disease (Slapped cheek syndrome) = erythema infectiosum 
•	Mild rash illness in normal children
Polyarthropy syndrome
•	In adults 
•	Can mimic rheumatoid arthritis 
Transient Aplastic Crisis
•	People with increased erythropoesis or hymolytic disorders
Hydrops fetalis 
•	Infection in infants
•	Congenital anemia 
Persistent anemia 
•	In immunocompromised patients = red cell aplasia

Question 4

HPV: transmission & pathogenesis

Answer 4

o Virtually everyone is seropositive
o Widespread in nature
o Sturdy and survive for long periods on surfaces

Transmitted by:
• Direct contact with contaminated objects
• Direct contact from people with warts
o Requires break in skin for access to basal epithelial cells of skin

Pathogenesis:
Virus infects basal epithelial cells in skin or mucous membranes
• Located on BM, serve as stem cells
• Viral DNA enters nucleus = latent site of infection
• Basal cells divide → daughter cells move away from BM
• Triggers differentiation process = activates viral life cycle
Early proteins expressed = Large T antigen protein
• Causes proliferation
• Dividing cells push up on cells above → wart forms
• Also: Large T stimulates viral DNA replication, late gene expression, viral assembly
• Verucous warts = virus changes keratin gene expression (hyperkeratosis)

Question 5

HPV: diagnosis

Answer 5

Physical appearance

PAP smear
• Looking for viral induced cytopathic effect in cervical epithelial cells

Colposcopy (but often not visual)

Acetowhite staining
• Apply dilute acetic acid solution
• Turns wart white due to altered keratin synthesis in infected cells
• Able to visualize

PCR
Extremely difficult to culture

Question 6

HPV: treatment

Answer 6

• OTC drugs
• Surgery
• Freezing
• Laser (but don’t breathe vapors → nasal papillomas)
• Podofilox (injection); Aldera (topical cream)
• IFNα = directly injected into wart
• Duct tape
• Spontaneously regression (associated with damage causing wart to bleed)

Question 7

HPV: prevention

Answer 7

• Avoid contact with contaminated areas
• Condoms (for genital warts)
• Careful because can have asymptomatic infection
• Can also be transmitted by oral sex
• Vaccine

Question 8

Molluscum Contagiosum: transmission

Answer 8

Close contact (including sexual activity)

Question 9

Molluscum Contagiosum: diagnosis

Answer 9

• Appearance of characteristic lesions

* Confirmed = biopsy and histological evaluation (Henderson-Paterson cells)

Question 10

Molluscum Contagiosum: treatment

Answer 10

• No vaccine
• Surgery, laser, freezing, electrodessication
• Antiviral (cidofovir) = no approved by FDA, used on limited basis
• For immune-deficient patients = restore immune status

Question 11

Parvovirus B19: transmission

Answer 11

• Respiratory secretions
• Close contact
• Relatively heat stable

Question 12

Parvovirus B19: diagnosis

Answer 12

• Usually based on IgM antigen capture assays (can be detected as much at 3 months later)
• Detect DNA in serum (by dot blotting or PCR)

Question 13

Parvovirus B19: treatment

Answer 13

No antivirals

Immunocompetent = mild and self-limiting
• Symptomatic treatment
• NSAIDS if arthralgia or arthritis
• Blood transfusions if anemia

Immune compromised
• Halt immune suppression by giving IV immunoglobulin

Question 14

Explain the role of Papilloma viruses in cancer.

Answer 14

• 70-80% are HPV 16 or 18
• HPV = immortalizes cells
• But needs other mutations for cancer development

Co-factors for cancer conversion:
o Sunlight for EV and squamous cell carcinoma
o X-rays for laryngeal papillomas (probably others)
o Cigarette smoke
o Other viruses? (HSV-2 has been shown to upregulate HPV gene expression)

All tumors = express E6 and E7
o E6 = binds p53 (recognized unscheduled DNA synthesis, halts cell division)
o E7 = interferes with retinoblastoma protein (regulates cell cycle)

All tumors = have integrated HPV DNA
o Disrupts E2
• Normally inhibits E6 and E7
• Result = continuous expression → proliferation

Question 15

Explain the nature of the HPV vaccine and its recommended use.

Answer 15

• Guardisil vaccine = HPV 6, 11, 16, & 18
• Recommended for teenage girls
o Also approved for males 9-26 years
• Currently optional
• Must be aware that vaccine not cover all possible viruses
• Won’t prevent common warts