Lecture 75 - Papilloma and Polyoma Viruses

Question 1

what are the common characteristics between Papilloma and Polyoma Viruses?

Answer 1

Structure: Naked icosohedrals

Double stranded circular DNA

Lytic, chronic, latent and transforming infections

Needs the host polymerase

Defined tissue tropisms

Question 2

Polyoma-viridae

• what are two important viruses to know?
• Epidemiology?
• Transmission?
• Structure?

Answer 2

BK and JC Virus

81% seropositivity

Respiratory transmission

Nake Icosohedral; circular dsDNA

Question 3

Polyoma Genome features:

• Early region
• late region

Answer 3

Early – large T antigen

• important for transcription; helps bind host polymerase with the promotor
• Also inactivates P53 and Rb

Late region – Structural genes (Vp1, 2,3)

Question 4

JC Virus

- clinical manifestation

Answer 4

Progressive Multifocal Leukoencephalopathy –

Occurs in immunocompromised
Virus makes way to CNS
attacks oligodendrocytes — lytic phase leads to myelin destruction

Symptoms: dyscoridation, gait imbalance, cognitive dysfunction, vision changes, paresis; can mimic MS

Question 5

BK Virus

• clinical manifestations

Answer 5

Multiplies in the UT

Associatd with nephropathy

hemorrhagic cystitis

Question 6

HPV

• what is the most clinically important genera?
• strucutre

Answer 6

Alpha Papillomavirus – cutaneous and mucosal disease

Naked Icosohedral
DsDNA

Question 7

High risk HPV types

Low Risk HPV types

Answer 7

High risk: 16 > 18 > 31, 33, 45, 52, 58
high grade lesions, cancer

Low Risk: 6, 11
low grade lesions, condylomas, papillomatosis

Question 8

HPV

Epidemiology

Answer 8

Most prevalent STD
79 Million people affected world wide

Highest inceidence in 15-24 yo

5% of cancers world wide
Cervical cancer
oropharyngeal cancer

Highest overall in MSM

Question 9

Transmission of HPV

Answer 9

Vaginal, anal, oral intercourse

Mother to child

Higher rates of transmssion from women to men

Most infections are transient (will clear in 2 years in 90% of cases)

Question 10

HPV Genome

Answer 10

8kb

Unidirectional Transcription

Three regions:
Long Control Region – noncoding; regulatory elements

Early – 6 open reading frames – genes for replication, tx, immortalization and growth

Late – 2 open reading frames; structural; L1 and L2 of the capsid

Question 11

Lifecycle of the HPV

Answer 11

“transcriptional cascade along squamous epithelial cell differentiation”

• Microtrauma – allows entry to the stratum basale; binds proteoglycan and integrans and engulfed via macroendocytosis
• Exists in the nucleus as an Episome
• Middle layers of the epidermis – early genes active. Genome amplification

Top layers – late genes activated; amplification and assembly
Very high copy number in the Keratinized layer

Release – virions released as dead cells keratinzed and shed. Not true lysis of the cell

Question 12

HPV Integration

functionally important protein which is lost upon integration? what is the effect?

Answer 12

Episomally
E2 is very active – inhibits E6 and E7.

Upon Integration – loss of E2 activity: loss of E6 and E7 inhibition

E6 – degrades p53
E7 - Degrades Rb
Therefore higher chance of malignancy after integration

Question 13

HPV Low grade Clinical Manifestations?

what HPV types are indicated ?

Answer 13

HPV 6, 11 – anogenital warts; may lead to CIN 1

HPV 1, 2, 4 - warts on hands and feet

HPV 6, 11, – cervical intreepithelail neoplasia (CIN1)
low grade lesions
not precancerous

HPV 6, 11 – Recurrent respiratory papillomatosis.
Rare
acquired via birth
Requires removal of reccurent llaryngeal tumors

Question 14

cancerous manifestations of HPV

• where do they occur histologically?

Answer 14

epithelial transformation zones
epithelium goes from Columnar to squamous

Cervical/Anal Intraepithelial neoplasia 2 (CIN/AIN 2)

• –Moderate dysplasia (no more than 2/3s of epithelium affected)
• • 40% regression
• -5% cancer

Cervical/anal Intraepithelial neoplasia 3 (CIN/AIN 3)

• -more dysplasia –more than 2/3s of epithelium affected; up to full thickness lesions
• -33% regression
• -12% cancer

Head and Neck cancer
-Tonsils, BOT and oropharynx
not necessarily transformation zones

Question 15

HPV Persistence:

-definition of persistence?
what proteins in what HPV types are more likely to cause cancer ?

Answer 15

HPV 16, 18

E6 and E7

Define: detection of same HPV type more than twice over 6-12 months

Longer they persist, higher chance of integration
higher chance of malignancy

Question 16

Diagnosis of HPV

Answer 16

○ Gold Standard: Molecular detection of RNA/DNA

Pathological Changes: Koilocytes

Culture and serology are difficult

Question 17

Treatment

Prevention – Primary vs secondary

Answer 17

• No treatment
• surgical removal of lesions

Primary Prevent: Abstinence, condoms, circumcision, HPV Vaccine

Secondary: Cervical/anal cancer screenings

Question 18

HPV Vaccines:

• structure
• what are the two types?

Answer 18

Structure: L1 protein grown in yeast cells; self assembles to form empty viral capsid

Ceravix – Bivalent – HPV 16, 18

Gardasil – Quadravalent – HPV 16, 18, 11, 6
- can be given to men