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Retrovirus-induced feline pure red blood cell aplasia: pathogenesis and response to suramin
1Department of Medicine, University of Washington, Seattle 98195.
Insights
Feline leukemia virus subgroup C/Sarma (FeLV-C/Sarma) impairs red blood cell production by blocking erythroid progenitor differentiation. Suramin treatment improved erythropoiesis without eliminating FeLV-C/Sarma infection in cats.
Area of Science:
- Veterinary Medicine
- Virology
- Hematology
Background:
- Feline leukemia virus subgroup C/Sarma (FeLV-C/Sarma) causes pure red blood cell aplasia in cats.
- Both erythroid (BFU-E, CFU-E) and granulocyte/macrophage (CFU-GM) progenitors are infected, but only erythropoiesis is affected.
Purpose of the Study:
- To investigate the mechanism by which FeLV-C/Sarma inhibits erythropoiesis.
- To correlate in vitro findings with in vivo disease progression.
- To explore potential therapeutic interventions.
Main Methods:
- Prospective studies in six cats infected with FeLV-C/Sarma.
- Analysis of erythroid and granulocyte/macrophage progenitor frequencies in marrow cultures.
- Administration of suramin to anemic cats and assessment of erythropoiesis.
Main Results:
- CFU-E became undetectable preceding anemia, while BFU-E persisted but lost responsiveness to growth factors.
- CFU-GM responses remained unchanged.
- Suramin treatment rapidly improved erythropoiesis and increased CFU-E counts, despite persistent progenitor infection.
Conclusions:
- FeLV-C/Sarma, likely via its gp70 envelope glycoprotein, inhibits BFU-E to CFU-E differentiation.
- Suramin modulates erythroid differentiation independently of progenitor infection.
- Understanding this mechanism offers insights into erythropoiesis regulation.
Abstract:
Feline leukemia virus, subgroup C/Sarma (FeLV-C/Sarma) induces pure red blood cell aplasia in cats. Although erythroid (BFU-E and CFU-E) and granulocyte/macrophage (CFU-GM) progenitors are infected with this virus, only erythropoiesis is impaired. Two to 3 weeks before the onset of anemia, CFU-E become undetectable in marrow cultures while earlier erythroid progenitors (BFU-E) persist, suggesting that FeLV-C/Sarma (presumably via its envelope glycoprotein gp70) inhibits the differentiation of BFU-E to CFU-E in vivo. To correlate in vitro observations with the progression of disease, prospective studies were performed in six cats. These studies showed that at the time that the frequencies of CFU-E decreased in marrow cultures, BFU-E no longer responded to hematopoietic growth factor(s), although the responses of CFU-GM were unchanged. In further studies, anemic cats received suramin, a reverse-transcriptase inhibitor with other diverse effects. Within 4 to 14 days, erythropoiesis improved and up to 1,616 CFU-E were detected per 10(5) marrow mononuclear cells. However, progenitor cells remained infected, suggesting that suramin modulated erythroid differentiation without inhibiting progenitor infection. These observations led to the hypothesis that the gp70 of FeLV-C/Sarma impairs BFU-E differentiation by interference with ligand/receptor interactions or signal transduction pathways unique to erythroid cells. Understanding this mechanism should provide insights into the interactions controlling early erythropoiesis.