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Human TK− cells carrying the HSV-2 TK gene as a result of transformation with virus DNA express a TK activity of virus origin and maintain the TK+ phenotype when grown in HAT medium. Under non-selective conditions, however, reversion to a TK− phenotype occurs with a significant frequency characteristic of each transformed line. Once reversion has occurred the TK− phenotype appears to be stable, since only very rare instances of TK− to TK+ reversion have been observed. TK− revertants were susceptible to re-transformation by virus DNA, but no reactivation of a silent virus TK gene could be obtained by superinfecting them with a TK− virus mutant. The data presented are consistent with the hypothesis that acquisition of the TK− phenotype is brought about by loss of the virus sequences coding for TK.
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