#40;病毒学教学课件）Celltransformationbyviruses.pptxVIP

Cell transformation by viruses;Outcomes of viral infection of a cell;Oncogenic Viruses;Approaches to study tumorigenesis in model systems;TABLE 2? The transformed cellular phenotype;Virus-induced transformation in cell culture;Cell growth regulation pathways;Cell transformation by RNA tumor viruses;Mechanisms of cell transformation by retroviruses;Viral Oncogenes;Mechanism of acquisition of cellular sequences by retroviruses -Infect the same cell with a wild type virus and a deleted virus -Insertion of deleted retrovirus upstream of a potential cellularoncogene -Chimeric RNA transcripts extend through the oncogene -Packaged chimeric RNA and wild type RNA into the same virion -During the next round infection, homologous recombination between chimeric RNA and wild type RNA;Ligand binding domains;Myc: transcriptional regulatory proteins;Myc and ErbB activation by insertion of avian leukosis virus;Oncogenesis of adult T cell leukemia (ATL) mediated by essential retroviral protein -No monoclonal insertion -Viral genome does not carry cellular oncogene -Very long latent period 一 20 years -Tax gene product 一 transcription activator HTLV?1;Nature hosts and experimental models by DNA tumor viruses;TABLE 5. Cellular targets ot th DNA tumor virus oncopfoteins;Homologous viral sequences involved in binding to the Rb family of proteins;Inactivation of RB-mediated control of E2F activity;Manipulate host cell machinery by large T antigen;Evolution of common strategies of the DNA tumor viruses -A diverse group of viruses -Inactivate Rb and p53 -Promote normal process of a productive infection 一 a S phase induction - viral DNA replication ? E1A S phase and p53 activation -E1B, T antigen and E6 block the action of p53;The E2Fl/ARF/Mdm2/p53 pathway G1 CDK —-—SV40 large T antigen Rb —\ 1 i p E2F1-----? p19ARF------1 Mdm2 ------1 p53 1 f p53 dependent genes 、「 S Phase Apoptosis Cell cycle arrest;Molecular mimicry of E5 transm