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Cydia pomonella granulovirus (CpGV) is a cornerstone of codling moth (Cydia pomonella) control in integrated and organic pome fruit production, though different types of resistance to CpGV products have been recorded in codling moth field populations in Europe for several years. Recently, a novel baculovirus named Cryptophlebia peltastica nucleopolyhedrovirus (CrpeNPV) was isolated from a laboratory culture of the litchi moth, Cryptophlebia peltastica, in South Africa. Along with CpGV, it is the third known baculovirus that is infectious to codling moth. In the present study, parameters of infectiveness of CrpeNPV, such as the median lethal concentration and median survival time, were determined for codling moth larvae susceptible or resistant to CpGV. In addition, the permissiveness of a codling moth cell line with respect to infection by CrpeNPV budded virus was demonstrated by infection and gene expression studies designed to investigate the complete replication cycle. Investigations of the high degree of virulence of CrpeNPV for codling moth larvae and cells are of high significant scientific and economic value and may offer new strategies for the biological control of susceptible and resistant populations of codling moth. IMPORTANCE The emergence of codling moth populations resistant to commercially applied isolates of CpGV is posing an imminent threat to organic pome fruit production. Very few CpGV isolates are left that are able to overcome the reported types of resistance, emphasizing the demand for new and highly virulent baculoviruses. Here we report the recently discovered CrpeNPV as highly infectious to all types of resistant codling moth populations with a high speed of killing, making it a promising candidate baculovirus in fighting the spread of resistant codling moth populations.