• Embed Doc
  • Copy Link
  • Readcast
  • Collections
  • CommentGo Back
Download
 
Note on Human Papillomaviruses and Polyomaviruses (1/2552) S. Saengamnatdej
1
Note on Papillomaviruses and Polyomaviruses
These two genera, which were once grouped together with vacuolating virusesin the same family of Papovavidae, are now classified separately.
Human health impact
●
associated with cervical cancer (at least 85% of cervical carcinomas contain integrated HPV-DNA.)
●
cause different kinds of warts such as
condylomata acuminata
found onthe vulva and cervix and in the vagina in women, and on penis shaft, peri-anal skin, and anal canal in men.
●
cause asymptomatic disease in healthy persons, but is reactivated tocause renal disease or PML, progressive multifocal leukoencephalopathy,in immunosuppressed
●
may oncogenically transform a nonpermissive cell.
Human papillomaviruses (HPV)
>100 types (genotypes, not serotypes, to distinguish by cross-hybridization)16 groups (A to P)Two types: Cutaneous & Mucosal HPV (seen in phylogenetic trees of E6 gene)
Virion features
1.icosahedral capsid 52-
55
nm, without envelope2.two structural proteins3.72 capsomeres4.circular d/b stranded DNA 8 kb5.7-8 early genes (E1-E8)6.2 late genes (L1-L2): (expressed only in terminally differentiated upper layers)7.All genes on plus strand
HPV pathogenesis
1.Species-specific DNA viruses2.Types are very tissue-specific3.Different diseases (warts, genital/ oral/ conjunctival papillomas)
 
Note on Human Papillomaviruses and Polyomaviruses (1/2552) S. Saengamnatdej
24.Lytic infections in permissive cells, but cause abortive, persistent, latent, or immortalize in nonpermissive cells5.Virus accesses the basal cell layer through breaks in the skin6.usually takes 3-4 months to develop warts.7.Viral infection remains local and generally regress spontaneously but canrecur.8.HPV infection is hidden from immune responses and persists9.Certain types are associated with dysplasia that may become cancerouswith the action of cofactors. (40-70% of the mild dysplasias spontaneouslyregress)10. DNA of specific HPV types is present (integrated) in the tumor cellchromosome11. HPV-1, 2, 3, and 4 infect hands and feet,12. HPV-6, 11, 16, 18, 31, 33, and 45 most commonly infect mucosalepithelium in anorectal tract & orolaryngeal cavity. (more than 30 types)13. HPV-2 & 57 infect skin & genital mucosa.14. HPV-16 associated with cervical cancer 15. In the following figure, genes E1&E2 are frequently disrupted byintegration and gene E5 is often lost or not expressed after integration
[1]
. 
 
Note on Human Papillomaviruses and Polyomaviruses (1/2552) S. Saengamnatdej
316.The virus-induced increase in cell number causes the basal and theprickle cell layer (stratum spinosum)
to thicken.
17. As the basal cell differentiates,
the specific nuclear factors
expressedin the different layers and types of skin and mucosa promote transcriptionof different viral genes.18. In a laryngeal papillomas, malignant conversion has been described,usually after radiotherapy to treat the initial lesion.
Immunity
Humoral and cell-mediated immunity developed.Regression is usually the result of cellular immunity.Cell-mediated immunodeficiency (1
°
or 2
°
) increases a risk of developingwarts which can be extensive, persistent or recurrent and likely to progress. In acase of selective depletion of specific T cell clones (rare genetic skin disorder 
epidermodysplasia verruciformis
, EV), for example, large plane warts from virustypes such as HPV5 and 8 develop and persist for life.
Genes (HPV-16)
E1 - binds at Ori >> promote viral DNA replication and has helicase activity.- episomal maintenance
[1]
E2 - binds DNA >> helps E1, activates viral mRNA synthesis (binds to anenhancer site on the LCR can upregulate transcription of E6 & E7.)Lack E3E4 - virion maturation
[1]
, disrupts cytokeratins to promote releaseE5 - (oncoprotein) activates EGF receptor to promote growth (Not all Pvspossess and E5 gene.)E6 - binds p53 and promotes its degradation
●
p53 functions to induce cellular arrest to allow repair of DNA damageE7 - binds and inactivates p105RB
●
responsible for immortalizing properties of HPV-16&18
●
Rb is required for terminal differentiation of keratinocytes. Binding toit prevents differentiation and allows continued cell growth and viralexpression.L1 - major capsid proteins (group- and type-specific determinants)L2 - minor capsid proteins (type-specific determinants)URR = upstream regulatory region (sometimes called LCR; long control region)
of 00

Leave a Comment

You must be to leave a comment.
Submit
Characters: ...
You must be to leave a comment.
Submit
Characters: ...