Professional Documents
Culture Documents
Papilloma Viruses
• Characteristics
– dsDNA viruses (circular)
– Genone 8 kbp
– Genome associated with cellular histones
– Naked capsid
• Widespread in humans and other animals
– They cause ‘warts’
– Some strains 16,18 and 31 associated with high risk of
cervical cancer
– Over 100 types of HVP found so far
Papilloma Viruses
• Different types infect different anatomical sites
– HPV-1 target feet
– HPV-2, 4, 7 hands
– Virus targets mucosa (oral, nasal, genital) OR skin
• Transmission of genital tract HPV thru sexual contact
• Transmission of skin HPV thru touching, or contaminated surface
• HPV that infect genital tract mucosal can cause
– cervical warts referred to as ‘condylomas’ (benign rarely progress to cancer)
– Strains 16,18 and 31 associated with high risk of cervical cancer such as
Squamous Cell Carcinoma
• Referred to as Oncogenic HPVs
• Genital tract infections are transient in many cases cause no symptoms
• Lack of symptoms allows for easier spreading
HPV 16
• HPV 16 is of interest due to oncogenic properties
• 6 Early genes (E1, E2, E4, E5, E6 and E7)
• 2 Late genes (L1 and L2)
• Genome has multiple ORFs
• Variable Splicing of mRNA transcripts yields variety of
mRNAs with multiple ORFs
– Virus targets mucosa (oral, nasal, genital) OR skin
• Transmission of genital tract HPV thru sexual contact
• Transmission of skin HPV thru touching, or
contaminated surface
Infectious Cycle
• Infection requires entry to NON-DIFFERENTIATED basal cells
• Virus binds to heparin and 6-integrin
• Virions are taken in by endocytosis
• Genome ends up inside nucleus
– Stays as circular DNA
– Does not incorporate itself into host genome
• Replication of genome occurs generating 50-100 copies
– Every cell division genome is duplicated and split equally between parent and
daughter cell
– This type of division is referred to as ‘plasmid replication’
• When Basal Cells become Keratinocytes burst of viral replication occurs
– This burst is called vegetative replication
– During this same period L1 and L2 genes are expressed producing capsids
– Release of assembled virions occurs during cell death
HPV 16, 31 Genome Structure
Replication surge is unusual given the fact that keratinocytes are terminally differentiated
and do not carry any significant DNA replication
E7 is responsible for this peculiarity, binds Rb resulting in release of E2F transcription
factor
E2F then participates in expression of a variety of genes involved in cell cycle
E7 binds Rb protein increasing cell cycling, essentially convincing keratinocytes to divide
Rb is a major tumor suppressor protein. Many retinoblastoma cancers are due to mutated Rb
E6 Eliminates p53