Akvr-1, a dominant murine leukemia virus restriction gene, is polymorphic in leukemia-prone wild mice

Abstract

We describe a restriction gene (Akvr-1, for AKR virus restriction) that is polymorphic for two alleles, Akvr-1(R)(restrictive) and Akvr-1(r)(susceptible), in a feral population of mice (Mus musculus domesticus) at a squab farm near Lake Casitas (LC) in southern California. Akvr-1(R) is a dominant allele that exhibits 100% penetrance in prevention of viremia of AKR endogenous retrovirus and of virus-mediated lymphoma in LC (Akvr-1(RR))XAKR F1 hybrids. The restriction phenotype segregates as a single Mendelian locus in backcrosses to AKR mice. Akvr-1(R) likewise is effective in restriction of NB-tropic Moloney murine leukemia virus-induced viremia and NB-tropic Friend virus-induced splenomegaly but fails to restrict expression or pathogenesis of LC-derived amphotropic retrovirus. Pleiotropic restriction of AKR, Friend, and Moloney ecotropic viruses, but not of amphotropic virus, suggests that the viral targets of Akvr-1 in the three ecotropic viruses are similar to each other and distinct from the target in the LC-amphotropic virus. The relationship of Akvr-1 to previously reported murine restriction loci Fv-1, Fv-2, and Fv-4 is discussed.