Retrovirus-induced feline pure red cell aplasia. Hematopoietic progenitors are infected with feline leukemia virus and erythroid burst-forming cells are uniquely sensitive to heterologous complement.

Abstract

Feline leukemia virus subgroup C/Sarma (FeLV-C) induces pure red cell aplasia (PRCA) in cats. Just before the onset of anemia, erythroid colony-forming cells (CFU-E) become undetectable in marrow culture, yet normal frequencies of erythroid burst-forming cells (BFU-E)-and granulocyte-macrophage colony-forming cells (CFU-GM) persist. To determine if erythroid progenitors were uniquely infected with retrovirus, marrow mononuclear cells from cats viremic with FeLV-C were labeled with monoclonal antibodies to gp7O and then analyzed with a fluorescence-activated cell sorter. Both erythroid and granulocyte-macrophage progenitors were among cells sorting positively, suggesting that infection of BFU-E alone did not result in PRCA. The results were confirmed by complement (C) lysis studies using baby rabbit or guinea pig sera as sources of C'. These studies also suggested that BFU-E from cats with PRCA were unusually sensitive to C' alone, without the addition of antibody. In further studies, we demonstrated that C' activation was via the classical pathway and that C' sensitivity was unique to BFU-E and not a property of CFU-E, CFU-GM, or progenitors that were capable of giving rise to BFU-E in suspension culture. As BFU-E from cats viremic with FeLV-A/Glasgow-1 or the Rickard strain of feline leukemia virus were not sensitive to C', this finding may relate to the pathogenesis of feline PRCA. We hypothesize that, in cats viremic with FeLV-C, the abnormal C' sensitivity of BFU-E leads to the absence of CFU-E and anemia.

Comprehensive Mapping of Receptor-Functioning Domains in Feline Leukemia Virus Subgroup C Receptor FLVCR1

“…3A, cell lysate blot). We also analyzed surface expression of [1][2] and found this protein to be weakly expressed on the surface (data not shown). Thus, the resistance of 1-2 ECL6 XCT-expressing cells and 1-2 TM10 -expressing cells to FeLV-C is likely caused by a severe disruption in the surface expression of these proteins.…”

“…This disease is characterized by a specific block in development of erythroid progenitor cells (1,8), which are important precursor cells for erythrocytes. Feline PRCA is caused by FeLV-C (1,8), which arises in infected cats from the weakly pathogenic progenitor FeLV subgroup A through mutations in the envelope gene responsible for receptor recognition (19,28). These studies have led to the hypothesis that PRCA is caused by interaction of FeLV-C envelope with its cell surface receptor.…”

Replication kinetics and cell tropism of an immunosuppressive feline leukaemia virus

“…SIVmac infects marrow myeloid cells of macaques, in which suppressed haemopoietic progenitor cell colony formation in vitro has been demonstrated (Watanabe et al, 1990). Subgroup C FeLV infects and depletes or suppresses erythroprogenitor cells, resulting in fatal red cell aplasia (Abkowitz et al, 1987;Dean e~ al., 1992;Hoover et al, 1974;Jarrett et al, 1984;Onions et al, 1982;Reidel et al, I986). Thus, oncoretrovirus infection of bone marrow progenitor cells appears to be common and may lead to several pathogenic consequences.…”

Enhanced alternative splicing of the FLVCR1 gene in Diamond Blackfan anemia disrupts FLVCR1 expression and function that are critical for erythropoiesis

“…[21][22][23] The feline anemia has been suggested to be caused by the FeLV-C envelope (Env) protein disrupting the cellular function of the heme exporter FLVCR1, 24 which is used as a receptor for entry by FeLV-C. [25][26][27][28][29] Disruption of FLVCR1 heme export function in human K562 erythroid cells induces apoptosis and disrupts K562 erythroid differentiation. 30 Furthermore, FLVCR1 null mice, despite dying in utero and having reduced levels of myeloid and lymphoid cells, 31 show a severe disruption in the development of erythroid colonyforming units (CFU-E), and have the craniofacial and limb deformities found in some DBA patients.…”