Pyv^S: A Dominantly Acting Gene in C3H/BiDa Mice Conferring Susceptibility to Tumor Induction by Polyoma Virus

Results in a previous report established the presence of dominant genetic factor(s) in C3H/BiDa mice which contributed to the unusually high susceptibility of this strain to polyoma virus-induced tumors (Freund et al. (1992) Virology 191, 724-731). Here we show that C57BR/cdJ mice, while identical to C3H/BiDa at the H-2 locus, are almost completely lacking in susceptibility. Analysis of crosses between these two H-2^k strains has shown that susceptibility is due to a single dominant autosomal gene, designated Pyv^S. On an H-2^k background, Pyv^S acts in a highly penetrant manner to confer susceptibility to induction of a broad range of tumors by the virus. Analysis of F1 mice between C3H/BiDa and the highly resistant C57BL/6 (H-2^b) strain shows that Pyv^S can partially overcome the immunologically mediated resistance associated with an H-2^b haplotype. Pyv^S does not encode cell receptors for the virus, nor does it affect levels of virus replication or anti-viral humoral responses in the host. Studies with early passage embryo fibroblasts in culture show that Pyv^S does not affect intracellular events essential for either productive infection or cell transformation by the virus. Pyv^S thus determines a generalized susceptibility of the host to polyoma-induced tumors but apparently does not act at the level of target cells for tumor induction.