The adenine DNA methyltransferase M.CviRI (TGCmA) gene from chlorella virus XZ-6E was cloned into the Autographa californica nuclear polyhedrosis virus (AcMNPV) genome and expressed in Spodoptera frugiperda insect cells under the control of two tandemly arranged viral promoters, the early ETL promoter and the late polyhedrin promoter. M.CviRI activity was first detected at 10 hr p.i and reached a maximum at 48 hr p.i. Viral DNA synthesized in insect cells infected with M.CviRI expressing virus (AcMTRI) was methylated at all TGCA sites. Unexpectedly, AcMTRI-infected cells lysed 48 hr earlier than wild-type AcMNPV-infected cells. Moreover, cellular DNA, but not viral DNA, from AcMTRI-infected cells was degraded to fragment sizes characteristic of apoptosis. These results suggest that M.CviRI methylation influences the onset of viral cytopathic effects and induces an apoptosis-like response.