Comparison of gamma and neutron radiation inactivation of influenza A virus.

Radiation inactivation of viral pathogens has potential application in sterilization and in the manufacture of biological reagents, including the production of non-infectious viral antigens. Viral inactivation by gamma radiation has been extensively investigated, but few direct comparisons to other qualities of radiation have been explored. Experiments were designed to examine direct radiation damage by both gamma photons (gamma) and neutrons (n) while minimizing methodological differences. Frozen samples of influenza A X31/H3N2 and PR8/H1N1 were exposed to gamma and n at doses between 0 and 15.6 kGy. Other experimental parameters, including dose-rate, were not varied. Virus titers were determined by tissue culture infectious dose (TCID(50)) and plaque forming unit (PFU) assays. D(10) values, kGy per log reduction, were calculated from these assays. PR8 D(10) values based on PFU assays were approximately 2 and 5 kGy for gamma and n exposures, respectively, and those based on TCID(50) were approximately 6 and 14 kGy. Similar results were obtained for the A/X31 strain. The data demonstrate that gamma was 2-3-fold more effective than n, with a relative biological effectiveness (RBE) range of 0.43-0.65. These neutron results are likely the first reported for a medically relevant virus. PAGE analysis of viral proteins and RNAs failed to show macromolecular damage. D(10) values were found to be similar to a broad summary of previously reported gamma inactivation values for other virus types. The dependence of the magnitudes of D(10) on titer assay in this study suggests that more than one titer method should be used to determine if complete inactivation has occurred.