Overview

Non-enveloped double stranded DNA (deoxyribonucleic acid) virus (resistant to heat & desiccation)
> 150 subtypes: novel type >10% dissimilarity, 2–10% is a subtype, & <2% is variant
Low-risk types → benign papillomas
High-risk types → oncogenic
Genus α → pathogenic in normal hosts/ genus β → Epidermodysplasia verruciformis /immunosuppression

Virology/ Pathogenesis

Capsid (L1, L2) → protects viral DNA (deoxyribonucleic acid) + enables virus binding
Genome (3 domains):
1. Upstream regulatory region → transcription & replication
2. Early region → life cycle genes
3. Late region → encodes capsid proteins
Virus is entirely dependent on host cellular machinery
Pathogenesis: Minor abrasion → viral invasion to basal keratinocytes (binding via L1 major capsid protein + heparan sulfate necessary for infection) → DNA (deoxyribonucleic acid) genome then established in nuclei of basal cells. Viral replication & gene expression linked to differentiation state of infected cells:
- E1/E2 genes → viral gene transcription & replication (expression lower in basal layer, higher is superficial layers)
- E5/E6/E7 → viral DNA (deoxyribonucleic acid) amplification
- E6/E7 → viral oncoproteins in high-risk HPV types. E6 facilitates destruction of p53 + activation of telomerase. E7 binds to underphosphorylated retinoblastoma tumor suppressor protein, liberating E2F transcription factor → DNA (deoxyribonucleic acid) replication + binding of histone deacetylases leading to centrosome abnormalities & chromosomal instability. Amplified genomes are then encapsulated by L1/L2 capsid proteins → generate infectious virions → shed with the cornified layer.
- E4 → disrupt intracellular filamentous network of keratinocytes → facilitate virus release from corneocytes

Human Papillomaviruses (HPV)