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Chapter 40 HPV Learning Objectives 1. What are the basic facts of HPV? What host enzyme are they reliant upon? How do you classify genotypes? What anogenital wart-causing strains are low risk for carcinoma? High risk? Small circular DNA (episome), nonenveloped lack DNA polymerase 10% different DNA from other HPV in a specific, highly conserved genome region 6, 11, 40, 42, 43, etc. 16, 18, 26, 31, 35, etc. 2. What does a lack of envelope mean in terms of transmissibility and durability? How does the virus spread? Aids transmissibility and makes them resistant to detergents, dessication, and heat usually by direct skin to skin contact, and even then it requires a skin break can also be spread by exfoliation onto inanimate objects 3. What is the result when HPV is transferred to a child during birth? What rare condition are the immunocompromised susceptible to? Respiratory papillomatosis (in larynx) Epidermodysplasia verruciformis 4. What protein maintains the episome in all types of HPV? Which protein is a transcription factor that regulates expression of viral genes? E1, also functions as a helicase which unwinds the dsDNA episome to initiate replication E2; also regulates other transcription factors and RNA polymerase [two--transcription] 5. Where does initial infection take place? How does viral reproduction occur? Final stage? Basal cell layer of the epithelium Replicates in concert with the keratinocyte differentiation program Viral DNA produces capsid proteins L1 and L2, fills them with DNA, and then the keratinocytes are shed 6. What type of immune deficiency is likely to result in multiple chronic warts? Defects in cell-mediated immunity, since these viruses hide in host cells 7. Which two proteins are always expressed in cervical cancer cells? What does each do? E6 and E7 (but not all E6s and E7s are “high risk” variants) i. Immortalize human keratinocytes and increase growth rate E6 ubiquitinates p53 and induces telomerase expression E7 inactivates Rb, which starts up the cell cycle by releasing E2F 8. How do you diagnose? What drug can be used to treat? Based on signs and symptoms, in research PCR can be used Pap smear with nucleic acid-based test; warts may be hard to visualize during routine pelvic exam Imiquimod destroys host cells and exposes the virus to the immune system 9. What is the active component of the HPV vaccine? Virus-like particles, which assemble spontaneously from pure L1 from recombinant E. coli