Influenza Virus Resistance of Wild Mice: Wild-Type and Mutant Mx Alleles Occur at Comparable Frequencies

The laboratory-reared progeny of wild Mus musculus domesticus from several places in Europe and from California were tested for resistance to experimental infection with influenza viruses and for the ability of their explanted macrophages to synthesize Mx protein in response to type I interferon. About 75% of these mice were resistant to influenza viruses and were able to synthesize Mx protein, as expected for mice carrying the influenza virus resistance allele Mx⁺ in either homozygous or heterozygous form. Resistance of wild mice was inherited as a single autosomal dominant trait which cosegregated with the ability to synthesize Mx protein. About 25% of the randomly bred wild mice failed to synthesize Mx protein and died after infection with influenza virus, very much like inbred mice homozygous for the Mx^- allele. We conclude that Mx⁺ and Mx^- alleles occur at roughly equal frequencies in wild mice and that some selective advantage for heterozygous individuals exists in the wild. This finding raises new questions about the physiological role of the Mx locus.