Q beta bacteriophage photoinactivated by methylene blue plus light involves inactivation of its genomic RNA

Methylene blue (MB) is being used as a sensitizer for the photodynamic inactivation of viral contaminants, including the human immunodeficiency virus, in blood and blood components used in medical treatment. We recently showed that oxygen-dependent photodynamic inactivation of the RNA bacteriophage Q beta with MB plus light (MB + L) is associated with the formation of 8-oxo-7,8-dihydroguanine, protein carbonyls, RNA-protein crosslinkages and minor amounts of RNA strand breaks. We report herein, with the use of infectious RNA assays, that the lethal lesions in Q beta phage following MB + L exposure can be accounted for, and thereby most likely reside in, the RNA component of the phage but that the protein component of the virion contributes to the inactivation. The formation of RNA-protein crosslinkages as the primary inactivating type of lesion is put forth as the most probable model of the inactivation mechanism due to the sensitivity with which RNA-protein crosslinks are formed in response to MB + L exposure and the expectation of the powerful inactivating power of this type of lesion.