Differential pathogenesis of lethal mousepox in congenic DBA/2 mice implicates natural killer cell receptor NKR-P1 in necrotizing hepatitis and the fifth component of complement in recruitment of circulating leukocytes to spleen.

Innate resistance of C57BL/6 (B6) mice to lethal mousepox is controlled by multiple genes. Previously, four resistance genes were localized to specific subchromosomal regions and transferred onto a susceptible DBA/2 (D2) background by serial backcrossing and intercrossing to produce congenic strains. Intraperitoneally inoculated ectromelia virus was uniformly lethal and achieved similar titers in B6 and D2 mice but elicited differential responses in liver, spleen, and circulating blood leukocytes. The distribution of these response phenotypes in congenic strains linked control of phenotypes with specific subchromosomal regions. D2.R1 mice, which carried a differential segment of chromosome 6, exhibited a B6 liver response and intermediate spleen and circulating leukocyte responses. D2.R2 and D2.R4 mice, which carried differential segments of chromosomes 2 and 1, respectively, exhibited a D2 liver response, a B6 spleen response, and an intermediate circulating leukocyte response. The localization of control of liver response phenotypes to chromosome 6 implicates cells that express natural killer (NK) cell receptor NKR-P1 alloantigens. The localization of control of spleen and circulating leukocyte responses to chromosomes 1, 2, and 6 implicates NK cells, the fifth component of complement, and a gene near the selectin gene complex in recruitment of circulating leukocytes to spleen.