(病毒学）Cell transformation by viruses教材课程.pptVIP

Cell transformation by viruses Paul ZhouInstitut Pasteur of Shanghai Outcomes of viral infection of a cell Productive infection results in cell death Productive infection results in no cell death (chronic infection) Nonproductive infection – no viral replication but non-survival of host 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) Oncogenic Viruses Approaches to study tumorigenesis in model systems Experimental animals, mainly rodents but also higher mammals, can be infected with tumor viruses or with viral vectors expressing viral oncoproteins. Some of these animals then develop tumors, depending on the site and method of delivery, the dosage, and the virus or vector being tested. Cell culture assays measure changes in proliferation and survival in vitro. Numerous cell types can be adapted to grow in culture, and under certain circumstances, their properties can be immortalized and/or transformed by expressing oncoproteins. Transformation is usually assessed through a series of assays such as focus formation, growth in soft agar, survival and growth in low serum. Transgenic or genetically modified mice are powerful tools for analyzing the effects of oncoprotein expression in an organismal setting. Oncoproteins can be expressed ectopically in specific tissues or cell types to assess their effects on tissue homeostasis. Gene knockout technology allows for the tissue-specific removal of cellular genes that may play a role in tumorigenesis. 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