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Severe and transient pancytopenia associated with a chronic arenavirus infection
K S Broomhall1, M Morin, D C Pevear
1Department of Biology, Rensselaer Polytechnic Institute, Troy, NY 12180.
Abstract:
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.
Insights
A docile Lymphocytic Choriomeningitis Virus (LCMV) strain caused immune-mediated hemolytic anemia in mice, evidenced by peripheral red blood cell destruction. Other blood cell count drops were due to bone marrow inhibition.
Area of Science:
- Virology
- Immunology
- Hematology
Background:
- Lymphocytic Choriomeningitis Virus (LCMV) typically causes severe central nervous system disease.
- A 'docile' LCMV strain was studied for its distinct pathological effects in C3HeB/FeJ mice.
Purpose of the Study:
- To investigate the hematological consequences of infection with a 'docile' LCMV strain.
- To elucidate the mechanisms behind anemia, leukopenia, and thrombocytopenia induced by this LCMV strain.
Main Methods:
- Hematological evaluation over 5 weeks post-infection.
- Analysis of red blood cell morphology, reticulocyte counts, and bone marrow hyperplasia.
- Iron-59 uptake studies to assess erythropoiesis.
- Assessment of cyclophosphamide treatment effects.
Main Results:
- All infected mice developed pancytopenia, most severe at 3 weeks.
- Anemia resulted from peripheral red blood cell destruction, not stem cell inhibition.
- Cyclophosphamide treatment prevented anemia, suggesting an immune-mediated mechanism.
- Late-onset leukopenia and thrombocytopenia were linked to bone marrow granulocyte and megakaryocyte inhibition.
Conclusions:
- The 'docile' LCMV strain induces an immune-mediated hemolytic anemia in C3HeB/FeJ mice.
- Distinct mechanisms underlie anemia (immune-mediated peripheral destruction) and other cytopenias (bone marrow inhibition).
- This LCMV strain offers a model for studying virus-induced immune-mediated hematological disorders.