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18 Cards in this Set
- Front
- Back
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HPV General |
most common viral infection
isolated from filtrate of wart tissue
primarily infects epithelial cells
180 isotypes 40-50 are STD
Responsible for 99% of cervical cancers, most penile and anogential cancers, 5% of human cancers are due to HPV
HPV burden is starting to decrease due to the vaccine and PAP smears |
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HPV virion |
non envelope virus
icosahedral capsid
no viral proteins encapsidated
Each capsomere is made up of 5 copies of viral protein L1
Capsomeres self assemble |
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HPV genome |
protein of the outer coat then 1 copy of viral genome
L1 and L2 are structural capsid proteins, E1 and E2 are involved in HPV replication and transcriptional. E6 and E7 are involved in immortalization and escape from cell cycle arrest and apoptosis
LCR contains viral origin of DNA replication and viral promoters for mRNA synthesis |
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Epidermis |
Basal cells are the ones that are replicating and differentiation is occuring as you become more superficial
Cornified layer is disulfide crossed and is a major source of protection
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Epidermis and HPV life cycle |
At cornified layers mature virus is released
granular layers; virus assembly
vegetatitve viral DNA replication and expression of late capsid protein L1 and L2
Spinous layer is expression of early protein E4 and E5
Basal cell is early infection and immediated early proteins |
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HPV DNA replication |
carried out through the function of cellular replication enzymes
Only enzyme encoded by HPV is the HPV E1 protein which is a DNA helicase/NTPase
E2 protein interacts with cellular DNA replication enzymes and uses them to drive replication of the viral DNA genoms |
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E6 and E7 |
immediate early proteins, involved in cellular immortalization
E7 results in immortalization of E7 results in more cells producing virus
Retinoblastoma protein keeps the cycle stuck in G1 via E7 binding to pRB
E6 degrades p53 which is what triggers apoptosis resulting in greater virus produced |
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p53 |
produced at high rate but kept at low levels but when stressed the concentration is allowed to build to high levels due to post translational mods and phosphorylation
is a transcriptions factor for p21 which when increased prevents prodution of cyclokinases |
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End result of E6 and E7 |
hyper proliferation of epidermal cells resulting in hyperkeratosis characteristic of warts |
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Recurrent respiratory HPV |
type 6 and 11, during vaginal birth a mother can pass along the virus which takes refuge in the respiratort tract of kids and must be sequentially removed until immune response can take it out |
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HPV and cancer |
HPV drive cells to become cancerous via genomic instability, E7 and E6 oncogenes
Constantly proliferating cells due to loss of Rb, lack of cell cycle control/DNA damage checkpoints (loss of p53 tumor supressor) lack of apoptosis due to loss of p53
E2 not being produced allows E6 and 7 to go overboard |
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HPV integration |
is an accident
cancer is not a normal part of the HPve life cycle |
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HPV stats |
at any time 20M in US have infections with 6M new cases a year allowing for these random integration events to occur |
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Cervical Dysplasi |
HPV 16 18 31 and 45 are most infectious serotypes |
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Frequency of HPV infections |
50% of males have HPV despite no physical manifestation
Women during a 4 yr prospective study nearly 50% of young women becmae infected with at least one of 12 high risk strains |
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HPV commensal virus? |
maybe it is only a disease causing when it enters in immunocompromised
HPV cancer is an unintended consequence of HPV infection and is far more rare then infection but still a major cause of disease |
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Treatment and Prevention |
HPV vaccine Gardasil has 6 11 16 18 L1proteins Cervaric is 16 and 18 |
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Pap Smear |
screens cervical cancer can do a colposcopy and conectomy |
