This study investigates the role of 5-methylcytosine (5mC) in the endogenization of giant viruses in *Amoebidium appalachense*, a protist closely related to animals. The authors found that *Amoebidium* exhibits both gene body and transposon methylation, with large hypermethylated regions derived from viral insertions, including hundreds of endogenized giant viruses contributing 14% of the encoded genes. Using inhibitors and functional genomic assays, they demonstrated that 5mC silences these viral insertions. Alternative *Amoebidium* isolates show polymorphic giant virus insertions, indicating a dynamic process of infection, endogenization, and purging. The study highlights the critical role of 5mC in the controlled co-existence of viral DNA in eukaryotic genomes, making *Amoebidium* a unique model for understanding the hybrid origins of eukaryotic genomes.This study investigates the role of 5-methylcytosine (5mC) in the endogenization of giant viruses in *Amoebidium appalachense*, a protist closely related to animals. The authors found that *Amoebidium* exhibits both gene body and transposon methylation, with large hypermethylated regions derived from viral insertions, including hundreds of endogenized giant viruses contributing 14% of the encoded genes. Using inhibitors and functional genomic assays, they demonstrated that 5mC silences these viral insertions. Alternative *Amoebidium* isolates show polymorphic giant virus insertions, indicating a dynamic process of infection, endogenization, and purging. The study highlights the critical role of 5mC in the controlled co-existence of viral DNA in eukaryotic genomes, making *Amoebidium* a unique model for understanding the hybrid origins of eukaryotic genomes.