HPV HSV-2 Sexual Trans.

Question 1

Compare the structure of HPV to HSV

Answer 1

HPV is a naked icosahedral capsid with stable virions, is easily transmitted, and has small circular double stranded DNA genome (8 kB) encoded by 8 genes.

HSV on the other hand is an enveloped virus, transmitted by close sexual contact. It has a large linear double stranded DNA genome (154 kB) for 74 genes.

Question 2

How do HPV and HSV differ in their presentation?

Answer 2

HPV - Infection is often asymptomatic, but it can cause warts in squamos or mucosal epithelium (genital, conjunctival, and oral). Can be a precursor for cancer of the cervix penis and anus.

HSV is a big guy, so it’s gonna hit a lot of areas.

• skin rashes
• vesicular lesions
• CNS infection
• Congenital herpes in the newborn

Question 3

Compare the viral cycles of HPV and HSV

Answer 3

With HPV, due to the capsid, we see a persistent infection. Viral DNA replication depends on promoting host cell entry into and DNA replication. Replication of the virus itself requires cell differentiation.

With HSV cause it has that weak envelope, it needs to hide (also, reactivation is usually sneaky and asymptomatic, think mysterious envelope):

• latency in neurons
• lytic replication in the epithelium

Question 4

What genetic results do we get from HPV?

Answer 4

Viral early genes E6 and E7 inactivate tumor supressor p53 and pRb respectively to promote S phase entry of host cells to support viral DNA replication

Question 5

What genetic goodies does HSV give?

Answer 5

This guy encodes viral DNA enzymes for limited DNA synthesis and viral replication in terminally differentiated, post mitotic neurons and robust replication in epithelial cells.

Question 6

How do we treat HPV vs HSV?

Answer 6

For HPV the only thing we can do is give a vaccines for the oncogenic subtypes.

For HSV, antiviral drugs like acyclovir can be activated by the viral thymidine kinase to inhibit DNA synthesis.

Question 7

What cancer types do we really worry about with HPV?

Answer 7

Linked to human cervical carcinoma in women and ano-genital cancers in gay men.

Question 8

What HPVs are linked to condyloma acuminatum?

Answer 8

6 and 11

Question 9

What HPVs are linked to genital malignancies?

Answer 9

16, 18, 31, 33

Question 10

What HPVs are linked to respiratory papillomas?

Answer 10

6 and 11

Question 11

Plantar warts are linked to what HPVs?

Answer 11

1, 2, 4

Question 12

What do we find in viruses with naked capsids like HPV and polio? What is the advantage of this delivery system?

Answer 12

• Proteins and nucleic acids

- Environmentally stable, can retain infectivity even if dried out, and spreads REALLY easily.

Question 13

Discuss the cycle of HPV through the epithelium

Answer 13

HPV is just a capsid with stuff so it gets highly restricted at first in its abilities, even though it infects so easy.

DNA is maintained kinda like a plasmid just near the chromosomes in basal cells that are undifferentiated. Early gene expression occurs here as the capsid releases contents and starts to use the machinery provided in the nucleus. These early gene products stimulate proliferation of the basal cells, causing the papilloma, allowing the virus to move upwards to the keratinocytes. Late gene products and lytic DNA replications occur only here in the keratinocytes.

Question 14

Discuss the genes of the HPV “plasmid” DNA system in the order they are used:

Answer 14

E6/E7 - Induce cells to enter pseudo S phase to delay differentiation and keep DNA replication machinery out and available.

E1 - Replication initiation

E2 - Transcription, replication, genome maintenence

E4 - Disrupt keratin filaments

E5 - Stimulate growth factor receptors

L1, L2 - Capsid proteins.

Question 15

Discuss when genes are expressed with HPV in regards to where the eukaryotic cell is in its cycle

Answer 15

G1 to S - E6/E7, early gene expression
S - Enzymes and protein for DNA replication
G2 - Late gene expression
M - Virus assembly and egress

Question 16

Phosphorylating RB does what?

Answer 16

releases E2F to activate DNA synthesis.

Question 17

High grade dysplasias and carcinomas from HPV transmitted sexually are due to what dysfunction?

Answer 17

Integration of viral genome with a disruption of the E1 and E2 gene.

E6 and E7 oncoproteins are maintained and expressed in progressed HPV tumors.

Question 18

We have multivalent HPV vaccines for:

Answer 18

16, 18, 6, 11

Also, L1 assembles spontaneously into DNA-free, virus like particles (VLPs) which display the conformational epitopes found on virions. Such particles are useful for prophylactic immunization.

Question 19

On cervical examination, a large, flat papule was observed that turned white with application of 4% acetic acid. The Pap smear from this 25-year-old sexually active woman had koilocytotic cells.

Diagnosis?

Answer 19

Cervical papilloma

Question 20

A 32-year-old woman presents for her routine Pap smear, which shows evidence of abnormal cells. A biopsy shows squamous cell carcinoma. PCR analysis of cellular DNA yields HPV-16 DNA.

Diagnosis?

Answer 20

Cervical carcinoma

Question 21

What happens with HPV in cervical carcinoma?

Answer 21

In cervical carcinoma, HPV 16 and 18 genomes are integrated into host cell DNA. The break in viral genome occurs in the E1/E2 region. Viral replication is disrupted.

Question 22

Acyclovir vs Ganciclovir

Answer 22

Acyclovir is activated by the viral TK. Causes chain termination of DNA elongation and inhibits viral DNA polymerase.

Ganciclovir is used for CMV, which does not have a viral TK but can still be inhibited. A protein kinase analogue is involved in activating it.

Question 23

How does Foscarnet work?

Answer 23

This is a pyrophosphate analog that binds directly to the pyrophosphate-binding sites of RNA or DNA polymerases. It does not need to be activated by cellular or viral kinases.

Given as treatment for CMV retinitis in AIDS patients receiving AZT therapy.

Has renal side effects.