Genetic determinants of lung virus titers and resistance to lethal Sendai virus pneumonia

C 57 BL/6J mice are resistant to lethal Sendai virus pneumonia and have lower lung virus titers than susceptible DBA/2J mice. Linkage between these phenotypes was tested indirectly in segregant hybrids. Sas-1, B2m, and b on chromosomes 1, 2, and 4 were linked to significant (P less than .05) differences in virus-induced mortality; d on chromosome 9 was associated with a similar but smaller difference (.1 greater than P greater than .05). Mean lung virus titers were higher in F1 X DBA/2J mice that were homozygous for DBA alleles at B2m, b, and d than in heterozygotes. The difference in lung virus titers was larger between mice that were dihomozygous/diheterozygous for paired combinations; B2m-d (P less than .02), B2m-b (P less than .06), and b-d (P less than .05) and largest between mice that were trihomozygous/triheterozygous for B2m-b-d (P less than .001). The distribution of virus titers among 22 recombinant inbred strains derived from C 57 BL/6J and DBA/2J progenitors indicated 1) that the loci linked to B2m, b, and d are among at least 4 loci that regulate lung virus titers, 2) that Sas-1 may be linked to a fourth locus, 3) that the C 57 BL/6J genome contains at least one susceptibility locus, possibly within H-2, and 4) that some of these loci may be expressed through natural killer cell activity.