Retrovirus-induced feline pure red blood cell aplasia: pathogenesis and response to suramin.
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.
Abkowitz
J L
JL
Department of Medicine, University of Washington, Seattle 98195.
D000595:Amino Acid Sequence; D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D002415:Cats; D003114:Colony-Forming Units Assay; D004912:Erythrocytes / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D005256:Leukemia Virus, Feline / Q000235:genetics / Q000472:pathogenicity*; D008969:Molecular Sequence Data; D012010:Red-Cell Aplasia, Pure / Q000097:blood* / Q000188:drug therapy / Q000382:microbiology / Q000473:pathology; D012689:Sequence Homology, Nucleic Acid; D013498:Suramin / Q000627:therapeutic use*; D014168:Transferrin / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics
D014168:Transferrin; D014764:Viral Proteins; D013498:Suramin