Papilloma & Polyoma Flashcards
What are common characteristics of Papillomaviruses and Polyomaviruses?
- Non-enveloped, small icosahedral capsid viruses
- double stranded circular DNA genome
- Uses host polymerase
What are the two major polyomaviruses?
JC virus and BK virus
What is the mode of transmission of polyomaviruses?
Respiratory
What regions are encoded by the polyomavirus genome?
Early, late, and non-coding regions
What do the polyomavirus early gene regions encode?
Non-capsid regulatory proteins: Large-T antigen, small-T antigen
What is the function of large T antigen?
Binds and inactivates p53 and Rb protein (tumor suppressor proteins, therefore has potential to cause cancer)
What do the polyomavirus late gene regions encode?
VP1, VP2, VP3 structural proteins (capsid)
What is the most common clinical presentation of polyomavirus?
Asymptomatic!
In what population will you see clinical disease due to polyomavirus?
Immunosuppressed
- HIV patients (CD4 <200)
- Transplant patients
- Monoclonal antibody therapy (natalizumab, rituximab)
What is the main target organ for primary viremia of polyomavirus?
Kidney (usually remains latent indefinitely in kidney unless reactivated by immunosuppression)
What is the clinical manifestation of JC virus?
Progressive multifocal leukoencephalopathy (PML)
What is the pathogenesis of PML?
JC virus infects oligodendrocytes and astrocytes, causing characteristic demyelinating lesions
What is the clinical manifestation of BK virus?
Polyomavirus-associated nephropathy and ureteral stenosis
Hemorrhagic cystitis
Which types of HPV are high risk (higher potential for maliganant progression)?
16 and 18 most prevalent
Also 31, 33, 45, 52, 58
Which types of HPV are low risk (usually cause benign papillomas aka warts)?
6 and 11
What population acquires most new infections of HPV?
15-24 year olds
What is the mode of transmission of HPV?
Vaginal/anal/oral intercourse and genital contact
Rare nonsexual transmission: mother to newborn, fomites
How does the capsid size and genome size of HPV compare to that of polyomavirus?
Slightly bigger
HPV: capsid = 55 nm, genome = 8 kb
Polyoma virus: capsid = 40 nm, genome = 5 kb
What regions are encoded by the HPV genome?
Long control region (LCR), early region, and late region
What does the early genome region of HPV encode?
Genes for replication and HPV viral oncogenes (E6 and E7)
What does the late genome region of HPV encode?
L1 and L2 = structural genes that form the capsid
What is the life cycle of HPV?
- Accesses basal cell layer of epithelium through microtrauma to mucosa or skin
- HPV interacts with integrins and gets engulfed
- Exists episomally in basal cells
- Early genes stimulate cell growth, facilitating replication of viral genome by host DNA polymerase when cells divide
- Virus induced increase in cell number causes basal layer and stratum spinosum to thicken (wart or papilloma)
- As basal cell differentiates, factors expressed in different layers of skin promote transcription of different viral genes (late genes expressed only in terminally differentiated upper layer)
How does HPV become malignant?
Viral DNA gets integrated into host DNA, causing a loss of E2
Without E2, get consitutive activation of HPV viral oncogenes E6 and E7, causing increased proliferation and decreased repair of secondary mutations
What is the function of E6?
Degradation of p53 tumor suppressor
What is the function of E7?
Degrade Rb proteins (normally control cell cycle entry)
What is clinical presentation of low risk types of HPV 6 and 11?
- Warty lesions, usually perianal or penile
- If contracted from birth canal, get recurrent respiratory papillomatosis
- Cervical/anal intraepithelial neoplasia grade 1 (mild)
What is clinical presentation of high risk types of HPV 16 and 18?
- Cervical/anal intraepithelial neoplasia grade 2 or 3 (moderate or severe)
How is HPV diagnosed?
Molecular detection of RNA/DNA = gold standard
Obtain specimen from pap smear or directed biopsy
What is treatment for HPV?
Infection does not require treatment, cellular changes associated with infection require treatment
- Observe at low grade abnormality
- Surgery and ablation of affected tissue and high grade abnormality
What are the two types of HPV vaccine?
Bivalent
Quadrivalent
What is the HPV vaccine composed of?
Recombinant DNA-generated L1 proteins that self-assemble into viral like particles (VLPs)
VLP is like empty shell of HPV
Which HPV vaccine is licensed for use in males?
Quadrivalent
