Other Important Viruses

Question 1

HPV Lifecycle

Answer 1

• Break in skin surface gives virus access to basal cells. Virus enters nucleus and remains as an episome.
• May cause latent infections. Lytic phase begins as cell differentiates / flattens out. Higher viral titers in outer skin layers.
• E6 / E7 and large T antigen genes (early genes) are found lower down and trigger proliferation. Late genes seen in outer surfaces of skin cells. Gene expression directly tied to host cell differentiation.

Question 2

Epidermodysplasia verruciformis (EV)

Answer 2

Flat macular red wart that develops in immunodeficient pxs. May convert to SCC when exposed to sunlight.

Question 3

HPV cancer
What strains cause cervical / penile cancer?
Bowen’s Disease
Throat cancer

Answer 3

• Cancer – starts out as wart, which requires a co-factor to become cancerous. Incubation period for cancer is long due to requirement of cofactors.
• Cervical / penile cancer: Most are caused by HPV 16 / 18 (high risk viruses).
• Bowen’s disease – SCC on the penis or labia
• Throat cancer – starts deep in tonsil cervices. Oral sex. HPV-16. Better survival than smoking-related throat cancer.

Question 4

Genetics of HPV

Answer 4

• All tumors have INTEGRATED HPV DNA. Integration disrupts E2, which normally inhibits E6 / 7 → immortalization of cells.
• Rb inhibits G1 → S. E7 regulates Rb function, taking it out of the system.
• Don’t have E2, so do have E7, so don’t have Rb, so G1→S
• P53 triggers apoptosis in cells w/ unscheduled DNA synthesis.
• HPV virus has E6 protein, which inactivates p53 → lack of apoptosis. This is just the immortalization step (NOT cancer yet). Need cofactor, which is why these tumors are monoclonal and take a while to develop.

Question 5

Cofactors (mutagens) for HPV cancer (4)

Answer 5

• Sunlight → squamous cell carcinoma in pxs w/ EV
• X-rays → laryngeal papillomas (may block airway)
• Cigarettes – Vaginal fluid has carcinogens in smokers. Bathing cervical cells in these chemicals.
• HSV2 may upregulate HPV gene expression

Question 6

Gardasil
What is it?
Population

Answer 6

HPV Vaccine, including 16 / 18

Recommended for males and females b/w age 9-26.

Question 7

Molluscum Contagiosum
Type of virus
Immunocompromised pxs
Diagnosis
Treatment (3 things)

Answer 7

• Poxvirus
• May spread / enlarge, mimicking SCC in immunocompromised. Common in AIDS.
• Diagnosis – appearance is most common. Biopsy shows Henderson-Paterson cells.
• Treatment
• Cantharidin – topical vesicant (causes blistering)
• Salicylic acid / lactic acid combo – keratolytic, inducing apoptosis of skin cells.
• Imiquimod – TLR agonist, triggering inflammation. Injected into lesion.

Question 8

3 main polyomaviruses

Treatment

Answer 8

• JC Virus – causes latent infection. Asymptomatic in immunocompetent. Causes progressive multifocal leukoencephalopathy (PML) in immunosuppressed pxs
• BK Virus – causes latent infection. May be shed in urine. Asymptomatic in immunocompetent. Causes organ transplant infections and graft rejections in immunosuppressed pxs.
• JC and BK are common w/ 90% seropositive by adulthood.
• Merkel Cell Associated Polyoma Virus → Merkel Cell Carcinoma (neuroendocrine cells in skin; quickly becomes metastatic). Tx w/ surgery, radiation, chemo.
• Therapy – no specific therapies / no vaccines. Restoring immune system is best.

Question 9

Parvovirus B19
Season
Transmission
Tropism
Diagnosis
Treatment

Answer 9

• Higher rates in later winter – early summer.
• Usually asymptomatic / mild (diseases on diff card)
• Transmitted by respiratory secretions and close contact.
• B19 likes to replicate in precursors to RBCs. Grows in people w/ increased erythropoietin.
• Diagnosis – IgM assays.
• Therapy
• Self-limiting in immunocompetent pxs.
• NSAIDs help for arthralgia / arthritis
• Blood transfusions may be necessary for pxs w/ anemia
• Stop immunosuppression by administering IVIG

Question 10

5 diseases caused by Parvovirus B19

Answer 10

• Erythema infectiousum / 5th Disease / Slapped Cheek Syndrome – mild rash on cheeks in kids. Self-limiting.
• Polyarthropy Syndrome – occurs in normal adults. Similar to rheumatoid arthritis.
• Transient aplastic crisis – Temporary halt in production of RBCs. Occurs in people w/ increased erythropoietin
• Hydrops fetalis – congenital anemia, may be lethal.
• Persistent anemia in immunocompromised pxs