Attenuated viruses and method of making the same

Abstract

Disclosed are attenuated viruses, not naturally occurring, that contain one or more additional methylation sites in the genome of the virus compared to the corresponding wild-type virus. Preferably, the methylation sites are added into the genome of the virus by introducing an additional CG segment into the genome by means of a silent mutation. The attenuated viruses are useful for producing an immune response, including both the production of antibodies in animals for diagnostic use and the induction of protective immunity in a subject. Pharmaceutical formulations and methods of making the attenuated viruses are also disclosed.