生化Virus and Tumorigenesis 肿瘤与病毒.pptx

Virus and TumorigenesisHPV SV-40 BK, JCHBV EBV KSHVHTLV-1HCVViruses Contributing to 15% of Human Cancers Worldwide DNA viruses: papovaviruses hepadnaviruses herpesviruses adenoviruses poxviruses RNA viruses:retrovirusesflavivirusesHuman Cancers Associated with Virus Infection HPV Cervical Carcinoma HBV HCVHepatocellular Carcinoma HTLV-1 Adult T cell Leukemia EBVBurkitt’s Lymphoma Hodgkin’s Disease PTLD Nasopharyngeal Carcinoma KSHV Kaposi’s Sarcoma How do viruses contribute to cancer? Integrations that cause activation or inactivation of oncogenes or tumor suppressors, respectively. Expression of viral genes that alter key signal transduction pathways Containing v-onc genes that induce proliferation，inhibit apoptosis, and alter signaling pathways. Viruses not kill cell, be tumorigenicEvidence for classifying a tumor virus Presence of part of viral genome in tumors and expression of some viral genes.In vitro infection leads to transformationGrowth in low serumGrowth in soft agar Identification of viral genes that transform cells in cultureInfection in animal model results in tumorsRNA TUMOR VIRUSESRetrovirus (with DNA phase)Permissive cells are transformedIntegration of viral cDNA genomeRequires expression of oncogenes HCV (no DNA phase) - chronic inflammationViral proteins interact with p53 and lead to cell proliferation and prevent apoptosisMechanisms of cell transformation by retroviruses1. Retroviral transduction of oncogene (transducing retrovirus)2. Oncogene activation by retroviral insertion (cis-acting retrovirus)3. Oncogenesis mediated by essential retrovirus proteins (trans-activating retrovirus)J. Michael Bishop Harold E. VarmusTransducing retroviruses Viruses “create” oncogenes by acquiring and modifying cellular proto-oncogenes (v-onc) v-onc not essential viral gene unrelated to viral replication Replication of retroviruses is not cytocidal, nor required for tumorigenes