clinical virology I Flashcards
viruses and cell transformation
what is transformation?
the introduction of inheritable changes into a cell causing changes in growth phenotype and immortalisation
what is the significance of observing transformation in vitro?
it correlates with tumour formation
transformed cells divide under conditions that normal cells don’t
which mechanisms do viruses have that facilitate transformation?
- viruses promote G1, the phase in which there is rapid growth, accumulation of mutations and emergence of a transformed phenotype
- prevention of cell homeostatic mechanisms to push the population back to G0
- prevention of apoptosis
why are primary cells unsuitable for a transformation assay?
they have genotypic/phenotypic variability, and a limited lifespan in culture
which cell line is often used for studying transformation?
NIH 3T3 mouse fibroblastic cell line
why is NIH 3T3 cell line used to study transformation?
- these are clonal cells capable of indefinite growth
- however, they normally show contact inhibition
- therefore, can tell when transformation has occurred
which three conditions can be observed in a transformation assay?
- focus forming assays - morphological alteration
- anchorage independent growth
- reduced serum requirements
what is the considered to be the mechanism of transformation?
a multistep process involving initiation, promotion and progression
why does carcinogenic virus infection not always result in cancer?
- virus acts in concert with other factors (genetic, immunological, environmental)
- transformation usually requires persistence of viral genome
how do viral oncogenes promote cancer?
- disrupt the normal cellular signal transduction pathways
- disrupt the function of tumour suppressor proteins
- this alters gene expression favour growth
give an example of an actively transforming retrovirus
rous sarcoma virus
give an example of a retrovirus causing transformation via insertion activation
avian leukosis virus
give an example of a transactivating retrovirus
human T cell leukaemia virus
how does rous sarcoma virus cause cancer?
- carries a copy of cellular gene src
- this is biochemically altered due to a deletion (active)
- cells grow uncontrollably
how does avian leukosis virus cause cancer?
- integration of virus near cellular oncogene
- stimulates growth and further mutation
- clonal tumours appear after a multistage latent period
