ABSTRACT
Resistance to the acute lethal disease caused by the docile strain of lymphocytic choriomeningitis (LCM) virus varies widely between different mouse strains. In order to study the inheritance of host influence on susceptibility to this strain of LCM virus, we crossed the F1 to the parent with the recessive disease phenotype. In all cases, susceptibility was dominant. In backcross progeny obtained from matings of parental strains differing in both major histocompatibility complex (MHC) and non-MHC (SWR; C3H), 90% of the challenged mice died, indicating that at least three loci controlled susceptibility to the disease. When the parental strains carried similar MHC haplotypes but dissimilar background genes (B10.BR; CBA), 78% of the backcross mice succumbed, indicating that at least two non-MHC loci influenced disease susceptibility. It is unlikely, however, that the same two non-MHC loci are critical in all genetic combinations, since F1 produced from two H-2 identical, resistant strains (B10.BR; C3H) were found to be fully susceptible. When congenic mice, differing only in the D-end of the MHC region, were analysed, 50% of the backcross animals died, indicating that one gene in the MHC region was important; segregation analysis comparing MHC serotype and disease outcome indicated the H-2D locus itself as the determining factor.
Subject(s)
Genes, MHC Class II , Genes, MHC Class I , Lymphocytic Choriomeningitis/genetics , Lymphocytic choriomeningitis virus/pathogenicity , Animals , Crosses, Genetic , Disease Susceptibility , Female , H-2 Antigens/genetics , Lymphocytic Choriomeningitis/etiology , Lymphocytic Choriomeningitis/immunology , Male , Mice , Mice, Inbred C3H , Mice, Inbred C57BL , Mice, Inbred CBA , Sex Factors , Species Specificity , VirulenceABSTRACT
A so-called 'docile' strain of Lymphocytic Choriomeningitis Virus (LCMV) lacks the ability to cause the fatal central nervous system syndrome, commonly associated with most other strains of this virus, in C3HeB/FeJ mice. Hematological evaluation during a 5 week period revealed that every mouse experienced a pancytopenia which was the most severe around three weeks post-infection. The abnormal red blood cell (RBC) morphology seen in the peripheral blood along with the increased reticulocyte count and marked erythroid hyperplasia in the bone marrow indicated peripheral destruction, rather than stem cell inhibition, as the mechanism causing the anemia. An increase in the 59Fe uptake into the blood confirmed the fact that there was no loss in the erythropoietic capabilities in these mice at this time. Although it was clear that the RBCs were being destroyed in the periphery, there was no evidence of a microangiopathic hemolytic anemia nor of a direct viral infection of these cells. Cyclophosphamide treatment, however, prevented the phenomenon. Thus, it seemed likely that the virus-induced hemolytic anemia in these mice was immune-mediated. The late, but not the early drop in the white blood cell counts and the thrombocytopenia, on the other hand, could be traced to granulocyte and megakaryocyte inhibition in the bone marrow.
