Summary
We have examined a non-lytic system (3T3) in which cells infected with the oncogenic virus SV40 do not support significant independent viral DNA replication. The infected 3T3 cells have two, rather different, possible fates. They may be only transiently infected, losing their SV40 T antigen and all other signs of viral presence in three or four generations, or they may become transformed, with the acquisition of SV40 T antigen synthesis as a heritable characteristic and the apparent integration of the SV40 genome in the cells. It appears that it is the occurrence of this process of integration that converts transient non-lytic infection to viral transformation.
Utilizing interferon to study the expression of SV40 genetic material in transiently infected and transformed cells, we have provided indirect evidence to support the hypothesis that integration is the physical linkage of SV40 and host cell DNA in such a manner that transcription of m-RNA occurs without interruption across the point of junction. Studies with interferon and the adenovirus-SV40 hybrid virus E46+ support this interpretation.
In cells infected with E46+ (in which the covalent linkage of SV40 and adenovirus DNA has been demonstrated) SV40 T antigen synthesis lost the interferon sensitivity characteristic of SV40 virus and acquired a relative interferon resistance indistinguishable from that of the adenovirus to whose DNA the SV40 DNA is linked. In cells simultaneously infected with non-hybrid adenoviruses and SV40, both SV40 and adenovirus
T antigens were synthesized, but the SV40 T antigen synthesis exhibited its characteristic sensitivity to interferon. It is predicted that host-viral hybrid m-RNA molecules are synthesized in the SV40 transformed 3T3 cells and that adenovirus-SV40 hybrid m-RNA molecules are synthesized in cells infected with the adenovirusSV40 hybrid virus E46+.
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Dedicated to ProfessorJohn F. Enders on the occasion of his 70th birthday.
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Oxman, M.N. Some behavioral studies of simian virus 40 (SV40). Archiv f Virusforschung 22, 171–187 (1967). https://doi.org/10.1007/BF01240512
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DOI: https://doi.org/10.1007/BF01240512