HPV Flashcards
Tropism of HPV
Epithelial cells of skin and mucosa
How does HPV recurrence occur?
HPV genome remains in basal layer of the skin in non-permissive cells (epithelial cells)
Despite most people becoming infected with an HPV genotype early in life, most of these infections don’t manifest as warts because:
Innate immunity keeps them in check
Low risk
6&11
High risk
16, 18, 31, 33
SPI
Sub-clinical papilloma infection; most likely HPV 16 or 18 pr 31 = HIGH RISK!!
Vaccine protein
L1 caspid protein
Required for development of cervical cancer over time
HPV 16 or 18
Capsid proteins
L1 and L2; self-assemble into caspid
Provides stability of HPV
Non-enveloped
Where does replication of HPV occur?
Permissive cells, like keratinocytes
What does HPV do in non-permissive cells?
Transforms them and incorporates part of their genome (always includes E6 and E7)
HPV genome in benign vs. malignant cells
Maintained extra-chromosomally in benign cells but part of genome is in malignant cells (always includes E6 and E7)
5 features of transformed (non-permissive) cells
- No longer contact inhibited
- No longer anchorage-dependent
- Don’t require growth factors
- Immortal
- Tumor formation
Function of early genes
Replication and assembly
Function of late genes
Structure, i.e. caspid proteins
E6 function
Degrades p53
E7 function
Inactivates Rb
E6 and E7 expression in transformed cells is (higher, lower) because:
Higher
Loss of E2
Genes that are always incorporated into transformed cell genome:
E6 and E7
Cells initially infected by HPV
Germinal cells of basal skin layer
Describe pathogenesis of a wart
- HPV infects germinal cells
- Germinal cells and non-permissive so they become transformed
- Germinal cells differentiate into keratinocytes and become permissive
- Virus replication and shedding
- Benign tumor (wart)
Why do warts tend to cluster?
Keratinocytes shed virus, which infects surrounding basal layer cells
Caused by HPV 6 & 11
Anogenital warts (condyloma acuminatum/plana) and infantile laryngeal papillomas
