Flashcards in Oncogenesis Deck (25):
Does viral oncogenesis occur with immunosuppression or with chronic inflammation?
how do viruses cause cancer?
indirectly--for hepatitis B and C
How do viruses directly cause cancer?
DNA viruses can cause cells to enter S phase for their own benefit--but if virus doesn't complete its life cycle and kill the cell, then viral proteins cause cell to override normal controls on growth
What viruses are associated w human cancer
HTLV1 (lentivirus)-T cell leukemia
Where does papillomavirus infect?
cutaneous and mucosal epithelia in hands, feet, anogenital tract
genome of papillomavirus
double stranded DNA
Describe HPV early and late genes
early: E1, E2 mediate replication and transcription of viral DNA. E4 helps virus egress. E5,6,7 deal w cellular growth
Late: L1 and L2 make up the capsid
What do E6 and E7 do?
neutralize p53 and Rb, the brakes of the cell cycle
What can a wart formed from HPV infection result in?
resolution, or latency
Where does HPV initially infect on a tissue level?
Where does virion assembly and release occur for HPV?
in the cornified, apical layers of epithelium
how does HPV change the tissue morphology?
normally, only stratrum basale cells replicate. but HPV stimulates the cell cycle and causes cells in stratum spinosum to replicate--causes cells to be cube shaped still in more apical layers and an overgrowth of tissue
What is the role of Rb protein?
brake that prevents cell from going into S phase.
when there's enough CDK/cyclin in G1, Rb is phosphorylated and inactivated
What does E7 of HPV do?
Binds to Rb and tags it for degradation
What does p53 do?
activated by inappropriate entry into the cell cycle
causes synthesis of CDK/cyclin inhibitors
stops cell cycle
also can induce apoptosis
What does E6 do?
recruits ubiquitin ligase, which targets p53 for degradation
induces expression of telomerase--cell immortality
What makes for high risk strains of HPV?
strong correlation btwn hisk risk and activity of E6 and E7 proteins
What is carcinoma with HPV associated with?
integration of the DNA into the host chromosome b/c it disrupts the E2 gene, which normally is a transcriptional repressor. now increased E6 and E7 expression
What causes cervical neoplasia?
Episomal HPV DNA and virus production
What causes invasive cancer?
integrated HPV DNA (however, no virus production)
What can you detect for someone with HPV infection?
initially, negative Pap
HPV DNA found
no E6/7 mRNA yet
L1 protein found
What diagnostic tests are used for cervical intraepithelial neoplasia and cervical carcinoma?
pap smear--cells that are rounded and appear in clumps
hybrid capture assay for detection of HPV DNA
Are there vaccines for HPV?
Yes-Capside protein L1--results in humoral immunity
What kind of structures do L1s form in the vaccine?
VLPs-virus like particles