Radiation-resistant and radiation-sensitive forms of host resistance to polyomavirus

Newborn mice of several inbred strains develop few or no tumors following i noculation with highly tumorigenic strains of polyomavirus. Here we show th at such resistant strains can be divided into two groups based on the respo nses of adult mice to radiation followed by virus inoculation. Most strains show a radiation-sensitive form of resistance (Rr-s) and develop tumors fo llowing radiation and virus challenge. This type of resistance has previous ly been recognized as immunological, based on T-cell responses against viru s-encoded neoantigen(s) expressed in tumor cells. Other strains exhibit a r adiation-resistant form of resistance (Rr-r) and fail to develop tumors whe n treated in the same manner. Three additional properties of Rr-r mice dist inguish them from Rr-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 resistan ce in crosses with a highly susceptible strain. The Rr-r phenotype reflects a constitutive nonimmunological type of resistance that is targeted to the virus and blocks its dissemination.