Microbiology-HPV, HSV-2

Question 1

A 27 year old woman presents with genital warts. What type of virus is likely causing her condition and why might she be at high risk for cervical cancer?

Answer 1

She most likely has HPV. It is an icosahedral non-enveloped dsDNA virus. She is at risk for cancer because viral genes E6 and E7 inactivation tumor suppressors p53 and Rb respectively, promoting S phase entry and DNA replication.

Question 2

A 27 year old man presents with vesicular lesions, a fever and nuchal rigidity. He has had eruptions of the vesicular lesions a couple times in the past few years. What type of virus is likely causing his condition and how could you treat him?

Answer 2

HSV-2 is an enveloped dsDNA virus. It encodes DNA enzymes for limited replication in neurons that allows for the latent neuronal phase. It encodes DNA enzymes with robust replication in epithelial cells that causes the lytic epithelial phase. Note that HSV-2 can also cause CNS infection.

Question 3

Why are viruses common causes of human cancer?

Answer 3

Some act as direct carcinogens w/viral oncogenes integrated into cancer cell DNA, some induce immunosuppression, chronic inflammation or activate ROS and/or NOS.

Question 4

Common cancer linked to HPV in men

Answer 4

Ano-genital cancer

Question 5

HPV serotypes that result in genital tract condyloma acuminatum

Answer 5

6 and 11

Question 6

HPV serotypes that result in genital malignancies

Answer 6

16, 18, 31

Question 7

HPV serotypes that result in respiratory papillomas in children

Answer 7

6, 11

Question 8

HPV serotypes that result in plantar warts

Answer 8

1, 2, 4

Question 9

Why can HPV be spread by skin to skin contact and not just sexual contact?

Answer 9

It is environmentally stable and released from epithelial cell lysis. Since it is non-enveloped it remains infectious despite drying out, digestion and detergent exposure.

Question 10

When are the early HPV genes expressed and when are the late HPV genes expressed in HPV replication?

Answer 10

HPV infects epithelial cells -> Plasmid expresses early genes (E1, E2, E6, E7) in basal cells -> Early genes stimulate proliferation of basal cells -> Late genes (L1, L2, E4) are expressed -> Lysis of differentiated keratinocytes in upper epithelium

Question 11

What are the early HPV and late HPV genes?

Answer 11

E1 (replication initiation), E2 (transcription), E4 (disruption of keratin), E5 (growth factors stimulated), L1 & L2 (capsid protein synthesis), E6 & E7 (push cells into S phase)

Question 12

What differentiates cervical intraepithelial neoplasia from invasive carcinoma?

Answer 12

CIN is confined to the epithelial basement membrane and virus is still being produced. Carcinoma breaches the basement membrane, no virus is being produced and HPV is integrated into the epithelial DNA.

Question 13

What cells would you find on Pap smear of this cervix?

Answer 13

Note the micropapillary and microconvoluted structure. Pap smear would show vacuolized epithelial cells indicating an HPV-infected cervix.

Question 14

How does HPV’s E7 protein cause cancer? E6?

Answer 14

E7 binds and inactivates Rb. This frees E2F to drive DNA transcription. E6 destroys p53 that allows for aberrant DNA replication with DNA that has damage in it.

Question 15

Aside from removing tumor suppressor genes, how is cancer growth promoted by viral infection?

Answer 15

Viral integration and retroviral oncogenes activate transcriptional activators and protooncogens respectively.

Question 16

HPV most often associated with cervical carcinoma

Answer 16

HPV-16 > 50% of the time

Question 17

What is the initiating event of viral infection that starts the path of carcinoma development?

Answer 17

Integration of the viral genome, disruption of E1/E2 and maintenance of E6/E7 genes.

Question 18

Koch’s postulates for viral oncogenesis

Answer 18

1) Virus associated w/specific malignancy 2) Virus present in each malignancy 3) Virus transforms target cells into cancer cells 4) High incidence of cancer in areas endemic with virus

Question 19

Tetravalent HPV vaccine (Gardasil) serotypes

Answer 19

16, 18, 6 and 11.

Question 20

Bivalent HPV vaccine (Cervarix) serotypes

Answer 20

16 and 11

Question 21

A woman presents with a large and flat papule on her cervix. It turned whit with application of 4% acetic acid. Her pap smear showed koilocytic cells. What is the diagnosis?

Answer 21

Cervical papilloma

Question 22

How do HSV-2 particles exit the cell they are finished replicating in?

Answer 22

They bud through nuclear membranes and into membranes of exocytic vesicles.

Question 23

What is the most common manifestation of HSV-2 infection?

Answer 23

Genital herpes is very common and usually resolves. Neonatal herpes is very rare and there is impaired fetal development.

Question 24

When is neonatal HSV-2 infection a high risk?

Answer 24

Primary (non reactivation) HSV-2 infection prior to child birth poses the highest risk.

Question 25

What therapies are available for treatment of herpes?

Answer 25

Acyclovir and ganciclovir (herpes thymidine kinase): incorporate into viral DNA where viral thymidine kinase is present and terminates DNA chains. Herpes DNA polymerase (PAA). Forscarnet (PFA): binds to the pyrophosphate-binding sites of RNA or DNA polymerases, it can also be used in CMV and AIDS.

Question 26

What do acyclovir, famcyclovir, gangcyclovir and valacyclovir all look like?

Answer 26

GTP.

Question 27

What virus does not have a viral thymidine kinase but can still be inhibited by ganciclovir?

Answer 27

CMV. It has a protein kinase homologue.

Question 28

Anti-viral drug that does not need to be activated by cellular or viral kinases and also has renal side effects.

Answer 28

Forscarnet.

Question 29

What proteins are turned off by E6 and E7?

Answer 29

E1 and E2