08-cell病毒学virus巴斯德研究所.pptVIP

Cell transformation and oncolysis by virus Paul ZhouInstitut Pasteur of Shanghai Outcomes of viral infection of a cell Nonproductive infection – no viral replication and host cell survival with or without viral genome persistent as episomal DNA or integrated into host genome (potential oncogenesis and/or latent infection) Nonproductive infection – no viral replication but non-survival of host cell Productive infection results in cell death Productive infection without cell death (chronic infection) Virus-induced transformation in cell culture Conversion of modern cancer research into a genetic science Oncogenic phenotype results from discrete changes in key cellular control genes and from corruption of normal cellular growth signal A single infectious virus particle is sufficient for transformation All or part of viral genome persists in the transformed cells (often no productive infection but at least part of viral genome is expressed Cell growth regulation pathways Mechanisms of cell transformation by RNA tumor viruses Cell culture – a quantitative science Reverse transcription and integration but without cytocidal action The ability to acquire and transduce cellular genetic material (temperature sensitive versus transformation defective mutants) The insertional activation of cellular genes by the integrated provirus HTLV-1 – the oncogenesis activity is due to Tax protein 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 cellular oncogene- 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 Myc and ErbB activation by insertion of avian Leukosis virus Oncogenesis mediated by essential retroviral protein Nature hosts and experimental models by DNA tumor viruses Ind