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

Summary 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, andb on chromosomes 1, 2, and 4 were linked to significant (P<.05) differences in virus-induced mortality;d on chromosome 9 was associated with a similar but smaller difference (.1>P>.05). Mean lung virus titers were higher in F₁ × DBA/2 J mice that were homozygous for DBA alleles atB2m, b, andd than in heterozygotes. The difference in lung virus titers was larger between mice that were dihomozygous/diheterozygous for paired combinations;B2m-d (P<.02),B2m-b (P<.06), andb–d (P<.05) and largest between mice that were trihomozygous/triheterozygous forB2m-b–d (P<.001). The distribution of virus titers among 22 recombinant inbred strains derived from C 57 BL/6 J and DBA/2 J progenitors indicated 1) that the loci linked toB2m, b, andd are among at least 4 loci that regulate lung virus titers, 2) thatSas-1 may be linked to a fourth locus, 3) that the C 57 BL/6 J 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.