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. 1987 Oct;80(4):1056–1063. doi: 10.1172/JCI113160

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.

J L Abkowitz 1, R D Holly 1, C K Grant 1
PMCID: PMC442346  PMID: 2821071

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 gp70 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.

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Selected References

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  1. Abkowitz J. L., Holly R. D., Segal G. M., Adamson J. W. Multilineage, non-species specific hematopoietic growth factor(s) elaborated by a feline fibroblast cell line: enhancement by virus infection. J Cell Physiol. 1986 Apr;127(1):189–196. doi: 10.1002/jcp.1041270123. [DOI] [PubMed] [Google Scholar]
  2. Abkowitz J. L., Ott R. L., Holly R. D., Adamson J. W. Lymphocytes and antibody in retrovirus-induced feline pure red cell aplasia. J Natl Cancer Inst. 1987 Jan;78(1):135–139. doi: 10.1093/jnci/78.1.135. [DOI] [PubMed] [Google Scholar]
  3. Abkowitz J. L., Ott R. L., Nakamura J. M., Steinmann L., Fialkow P. J., Adamson J. W. Feline glucose-6-phosphate dehydrogenase cellular mosaicism. Application to the study of retrovirus-induced pure red cell aplasia. J Clin Invest. 1985 Jan;75(1):133–140. doi: 10.1172/JCI111665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baker P. J., Osofsky S. G. Activation of human complement by heat-killed, human kidney cells grown in cell culture. J Immunol. 1980 Jan;124(1):81–86. [PubMed] [Google Scholar]
  5. Bartholomew R. M., Esser A. F., Müller-Eberhard H. J. Lysis of oncornaviruses by human serum. Isolation of the viral complement (C1) receptor and identification as p15E. J Exp Med. 1978 Mar 1;147(3):844–853. doi: 10.1084/jem.147.3.844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cooper N. R., Jensen F. C., Welsh R. M., Jr, Oldstone M. B. Lysis of RNA tumor viruses by human serum: direct antibody-independent triggering of the classical complement pathway. J Exp Med. 1976 Oct 1;144(4):970–984. doi: 10.1084/jem.144.4.970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cooper N. R., Nemerow G. R. Complement, viruses, and virus-infected cells. Springer Semin Immunopathol. 1983;6(4):327–347. doi: 10.1007/BF02116278. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dessypris E. N., Clark D. A., McKee L. C., Jr, Krantz S. B. Increased sensitivity to complement or erythroid and myeloid progenitors in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1983 Sep 22;309(12):690–693. doi: 10.1056/NEJM198309223091202. [DOI] [PubMed] [Google Scholar]
  9. Dick J. E., Magli M. C., Huszar D., Phillips R. A., Bernstein A. Introduction of a selectable gene into primitive stem cells capable of long-term reconstitution of the hemopoietic system of W/Wv mice. Cell. 1985 Aug;42(1):71–79. doi: 10.1016/s0092-8674(85)80102-1. [DOI] [PubMed] [Google Scholar]
  10. Grant C. K., DeBoer D. J., Essex M., Worley M. B., Higgins J. Antibodies from healthy cats exposed to feline leukemia virus lyse feline lymphoma cells slowly with cat complement. J Immunol. 1977 Aug;119(2):401–406. [PubMed] [Google Scholar]
  11. Grant C. K., Ernisse B. J., Jarrett O., Jones F. R. Feline leukemia virus envelope gp70 of subgroups B and C defined by monoclonal antibodies with cytotoxic and neutralizing functions. J Immunol. 1983 Dec;131(6):3042–3048. [PubMed] [Google Scholar]
  12. Grant C. K., Pickard D. K., Ramaika C., Madewell B. R., Essex M. Complement and tumor antibody levels in cats, and changes associated with natural feline leukemia virus infection and malignant disease. Cancer Res. 1979 Jan;39(1):75–81. [PubMed] [Google Scholar]
  13. Ham T. H., Dingle J. H. STUDIES ON DESTRUCTION OF RED BLOOD CELLS. II. CHRONIC HEMOLYTIC ANEMIA WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA: CERTAIN IMMUNOLOGICAL ASPECTS OF THE HEMOLYTIC MECHANISM WITH SPECIAL REFERENCE TO SERUM COMPLEMENT. J Clin Invest. 1939 Nov;18(6):657–672. doi: 10.1172/JCI101081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hartmann R. C., Jenkins D. E. The "sugar-water" test for paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1966 Jul 21;275(3):155–157. doi: 10.1056/NEJM196607212750308. [DOI] [PubMed] [Google Scholar]
  15. Hock R. A., Miller A. D. Retrovirus-mediated transfer and expression of drug resistance genes in human haematopoietic progenitor cells. Nature. 1986 Mar 20;320(6059):275–277. doi: 10.1038/320275a0. [DOI] [PubMed] [Google Scholar]
  16. Jarrett O., Golder M. C., Toth S., Onions D. E., Stewart M. F. Interaction between feline leukaemia virus subgroups in the pathogenesis of erythroid hypoplasia. Int J Cancer. 1984 Aug 15;34(2):283–288. doi: 10.1002/ijc.2910340222. [DOI] [PubMed] [Google Scholar]
  17. Kunstling T. R., Rosse W. F. Erythrocyte acetylcholinesterase deficiency in paroxysmal nocturnal hemoglobinuria (PNH). A comparison of the complement-sensitive and insensitive populations. Blood. 1969 Apr;33(4):607–616. [PubMed] [Google Scholar]
  18. Lewis S. M., Dacie J. V. The aplastic anaemia--paroxysmal nocturnal haemoglobinuria syndrome. Br J Haematol. 1967 Mar;13(2):236–251. doi: 10.1111/j.1365-2141.1967.tb08736.x. [DOI] [PubMed] [Google Scholar]
  19. Maggio L., Hoffman R., Cotter S. M., Dainiak N., Mooney S., Maffei L. A. Feline preleukemia: an animal model of human disease. Yale J Biol Med. 1978 Jul-Aug;51(4):469–476. [PMC free article] [PubMed] [Google Scholar]
  20. Marcelletti J., Furmanski P. Infection of macrophages with Friend virus: relationship to the spontaneous regression of viral erythroleukemia. Cell. 1979 Mar;16(3):649–659. doi: 10.1016/0092-8674(79)90038-2. [DOI] [PubMed] [Google Scholar]
  21. Moore J. G., Humphries R. K., Frank M. M., Young N. Characterization of the hematopoietic defect in paroxysmal nocturnal hemoglobinuria. Exp Hematol. 1986 Mar;14(3):222–229. [PubMed] [Google Scholar]
  22. Mortimer P. P., Humphries R. K., Moore J. G., Purcell R. H., Young N. S. A human parvovirus-like virus inhibits haematopoietic colony formation in vitro. 1983 Mar 31-Apr 6Nature. 302(5907):426–429. doi: 10.1038/302426a0. [DOI] [PubMed] [Google Scholar]
  23. Mullins J. I., Chen C. S., Hoover E. A. Disease-specific and tissue-specific production of unintegrated feline leukaemia virus variant DNA in feline AIDS. Nature. 1986 Jan 23;319(6051):333–336. doi: 10.1038/319333a0. [DOI] [PubMed] [Google Scholar]
  24. Nicholson-Weller A., March J. P., Rosenfeld S. I., Austen K. F. Affected erythrocytes of patients with paroxysmal nocturnal hemoglobinuria are deficient in the complement regulatory protein, decay accelerating factor. Proc Natl Acad Sci U S A. 1983 Aug;80(16):5066–5070. doi: 10.1073/pnas.80.16.5066. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Nicholson-Weller A., Spicer D. B., Austen K. F. Deficiency of the complement regulatory protein, "decay-accelerating factor," on membranes of granulocytes, monocytes, and platelets in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1985 Apr 25;312(17):1091–1097. doi: 10.1056/NEJM198504253121704. [DOI] [PubMed] [Google Scholar]
  26. Oni S. B., Osunkoya B. O., Luzzatto L. Paroxysmal nocturnal hemoglobinuria: evidence for monoclonal origin of abnormal red cells. Blood. 1970 Aug;36(2):145–152. [PubMed] [Google Scholar]
  27. Onions D., Jarrett O., Testa N., Frassoni F., Toth S. Selective effect of feline leukaemia virus on early erythroid precursors. Nature. 1982 Mar 11;296(5853):156–158. doi: 10.1038/296156a0. [DOI] [PubMed] [Google Scholar]
  28. Rickard C. G., Post J. E., Noronha F., Barr L. M. A transmissible virus-induced lymphocytic leukemia of the cat. J Natl Cancer Inst. 1969 Jun;42(6):987–1014. [PubMed] [Google Scholar]
  29. Rosse W. F., Parker C. J. Paroxysmal nocturnal haemoglobinuria. Clin Haematol. 1985 Feb;14(1):105–125. [PubMed] [Google Scholar]
  30. Rosse W. F. Paroxysmal nocturnal hemoglobinuria--present status and future prospects. West J Med. 1980 Mar;132(3):219–228. [PMC free article] [PubMed] [Google Scholar]
  31. Testa N. G., Onions D., Jarrett O., Frassoni F., Eliason J. F. Haemopoietic colony formation (BFU-E, GM-CFC) during the development of pure red cell hypoplasia induced in the cat by feline leukaemia virus. Leuk Res. 1983;7(2):103–116. doi: 10.1016/0145-2126(83)90001-2. [DOI] [PubMed] [Google Scholar]
  32. Welsh R. M., Jr, Jensen F. C., Cooper N. R., Oldstone M. B. Inactivation of lysis of oncornaviruses by human serum. Virology. 1976 Oct 15;74(2):432–440. doi: 10.1016/0042-6822(76)90349-4. [DOI] [PubMed] [Google Scholar]
  33. Young N. S., Mortimer P. P., Moore J. G., Humphries R. K. Characterization of a virus that causes transient aplastic crisis. J Clin Invest. 1984 Jan;73(1):224–230. doi: 10.1172/JCI111195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Young N., Harrison M., Moore J., Mortimer P., Humphries R. K. Direct demonstration of the human parvovirus in erythroid progenitor cells infected in vitro. J Clin Invest. 1984 Dec;74(6):2024–2032. doi: 10.1172/JCI111625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Young N., Mortimer P. Viruses and bone marrow failure. Blood. 1984 Apr;63(4):729–737. [PubMed] [Google Scholar]

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