TumorViruslecture2010__培训课件.ppt

* * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * Inappropriate activation of cell cycle * Inappropriate activation of cell cycle Apoptosis * Inappropriate activation of cell cycle Apoptosis e.g. Overexpression of E2F1 or c-Myc induces cell cycle and apoptosis Defense mechanism against rogue proliferating cells? * Inappropriate activation of cell cycle Apoptosis e.g. - Overexpression of E2F1 or c-Myc induces cell cycle and apoptosis - Same is true for over-expression of Adenovirus E1A or HPV E7 * Encode early genes that inhibit apoptosis Adenovirus E1B HPV E6 SV40 T Ag * SV40 and HPV * Adenovirus E1B is Bcl2 family member - blocks function of pro-apoptotic Bcl2 family members through dimerization * Summary Small DNA tumor viruses usually replicate in episomal form but are found integrated in viral associated tumors Early genes promote cell cycle progression and prevent apoptosis Adenovirus - E1A (cell cycle) and E1B (apoptosis) HPV - E7 (cell cycle) and E6 (apoptosis) SV40 - T Ag (cell cycle and apoptosis) * Herpes viruses Oncogenic members: Epstein Barr virus (EBV) Kaposi’s Sarcoma Herpes virus (KSHV) Oncogenic mechanisms are distinct from small DNA tumor viruses - Don’t need to integrate - Cell cycle is not driven by lytic replication regulatory genes * Herpes viruses Hallmark of herpesviruses: * Herpes viruses Hallmark of herpesviruses: Existence of latent stage (in addition to lytic/replicative stage) * Herpes viruses Lytic replication phase for herpesviruses: * Herpes viruses Lytic replication phase for herpesviruses: - Herpesviruses are large and encode 80-100 lytic associated genes - Encode their own DNA polymerase and replication accessory enzymes - Therefore, they don’t require an S-phase environment for replication - Encode early genes that induce cell cycle arrest * Herpes viruses Latency: - Small subset of viral genes are expressed t