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

Abstract

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.

Sendai virus-induced alterations in lung structure/function correlate with viral loads and reveal a wide resistance/susceptibility spectrum among mouse strains

“…The results show that 1) the strain affects the maximum viral titer, 2) the strain affects the decrease in viral titer from day 5 to day 7, 3) there is no absolute correlation between the maximum titer and the decrease in viral titers, and 4) SeV pulmonary pantropism correlates with highest severity. In general, with two exceptions (14,15), the data and interpretations available in the literature led most authors to conclude that the maximum titer was not affected by the strain, whereas mortality and lesion and symptom severity were (9,13,23). Conversely, our results suggest that there is indeed a connection between the pulmonary titers and the morphological and clinical characteristics of the infection.…”

“…Several mouse strains were previously claimed to differ in resistance to SeV infection (9,11,(13)(14)(15)23). Subsequent studies based on those phenotypic differences generated an array of hypotheses about associated characteristics (sex, coat color) or underlying gene polymorphisms (interferon, H-2 haplotype, mucociliary transport, or Sas-1 loci), none of which were finally confirmed (9,11,(13)(14)(15).…”

“…Several mouse strains were previously claimed to differ in resistance to SeV infection (9,11,(13)(14)(15)23). Subsequent studies based on those phenotypic differences generated an array of hypotheses about associated characteristics (sex, coat color) or underlying gene polymorphisms (interferon, H-2 haplotype, mucociliary transport, or Sas-1 loci), none of which were finally confirmed (9,11,(13)(14)(15). To evaluate the possibility that using other strains could offer new avenues to identify the genes involved, we compared SeV infections among six strains that were deliberately chosen because they originated from different lineages, as deduced from known genealogical and phylogenetic data (6).…”

Differential antigen burden modulates the gamma interferon but not the immunoglobulin response in mice that vary in susceptibility to Sendai virus pneumonia

“…Inbred mice show diverse patterns of susceptibility to Sendai virus pneumonia (6,38). Genetic resistance to Sendai virus infection is multifactorial and autosomal, being largely determined by loci that do not map to the major histocompatibility complex (4,6). Otherwise, the mechanisms underlying inherited resistance are, as with many viruses, poorly understood.…”