Radiation-Resistant and Radiation-Sensitive Forms of Host Resistance to Polyomavirus

Newborn mice of several inbred strains develop few or no tumors following inoculation with highly tumorigenic strains of polyomavirus. Here we show that such resistant strains can be divided into two groups based on the responses of adult mice to radiation followed by virus inoculation. Most strains show a radiation-sensitive form of resistance (R(r-s)) and develop tumors following radiation and virus challenge. This type of resistance has previously been recognized as immunological, based on T-cell responses against virus-encoded neoantigen(s) expressed in tumor cells. Other strains exhibit a radiation-resistant form of resistance (R(r-r)) and fail to develop tumors when treated in the same manner. Three additional properties of R(r-r) mice distinguish them from R(r-s) mice: (i) survival of newborns following inoculation with a highly virulent and usually lethal strain of virus, (ii) resistance to virus spread in newborns inoculated with either tumorigenic or virulent virus strains, and (iii) dominant or semidominant transmission of resistance in crosses with a highly susceptible strain. The R(r-r) phenotype reflects a constitutive nonimmunological type of resistance that is targeted to the virus and blocks its dissemination.