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. 1991 Aug;65(8):4461–4469. doi: 10.1128/jvi.65.8.4461-4469.1991

Viral genetic determinants of T-cell killing and immunodeficiency disease induction by the feline leukemia virus FeLV-FAIDS.

P R Donahue 1, S L Quackenbush 1, M V Gallo 1, C M deNoronha 1, J Overbaugh 1, E A Hoover 1, J I Mullins 1
PMCID: PMC248886  PMID: 1649341

Abstract

Within the fatal immunodeficiency disease-inducing strain of feline leukemia virus, FeLV-FAIDS, are viruses which range in pathogenicity from minimally (clone 61E is the prototype) to acutely pathogenic, most of the latter of which are also replication defective (clone 61C is the prototype). Mixtures of 61E and 61C virus and chimeras generated between them, but not 61E alone, killed feline T cells. T-cell killing depended on changes within a 7-amino-acid region near the C terminus of the gp70 env gene or was achieved independently by changes within a 109-amino-acid region encompassing the N terminus of gp70. The carboxy-terminal change was also sufficient for induction of fatal immunodeficiency disease in cats. Other changes within the 61C gp70 gene enhanced T-cell killing, as did changes in the long terminal repeat, the latter of which also enhanced virus replication. T-cell killing correlated with high levels of intracellular unintegrated and proviral DNA, all of which were blocked by treatment of infected cells with sera from 61C-immune cats or with a neutralizing monoclonal antibody. These findings indicate that T-cell killing is a consequence of superinfection and that the mutations in env critical to pathogenicity of the immunosuppressive variant result in a failure to establish superinfection interference in infected cells.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson L. J., Jarrett W. F., Jarrett O., Laird H. M. Feline leukemia-virus infection of kittens: mortality associated with atrophy of the thymus and lymphoid depletion. J Natl Cancer Inst. 1971 Oct;47(4):807–817. [PubMed] [Google Scholar]
  2. Delwart E. L., Panganiban A. T. Role of reticuloendotheliosis virus envelope glycoprotein in superinfection interference. J Virol. 1989 Jan;63(1):273–280. doi: 10.1128/jvi.63.1.273-280.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dewhurst S., Embretson J. E., Anderson D. C., Mullins J. I., Fultz P. N. Sequence analysis and acute pathogenicity of molecularly cloned SIVSMM-PBj14. Nature. 1990 Jun 14;345(6276):636–640. doi: 10.1038/345636a0. [DOI] [PubMed] [Google Scholar]
  4. Donahue P. R., Hoover E. A., Beltz G. A., Riedel N., Hirsch V. M., Overbaugh J., Mullins J. I. Strong sequence conservation among horizontally transmissible, minimally pathogenic feline leukemia viruses. J Virol. 1988 Mar;62(3):722–731. doi: 10.1128/jvi.62.3.722-731.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dorner A. J., Coffin J. M. Determinants for receptor interaction and cell killing on the avian retrovirus glycoprotein gp85. Cell. 1986 May 9;45(3):365–374. doi: 10.1016/0092-8674(86)90322-3. [DOI] [PubMed] [Google Scholar]
  6. Dornsife R. E., Gasper P. W., Mullins J. I., Hoover E. A. Induction of aplastic anemia by intra-bone marrow inoculation of a molecularly cloned feline retrovirus. Leuk Res. 1989;13(9):745–755. doi: 10.1016/0145-2126(89)90087-8. [DOI] [PubMed] [Google Scholar]
  7. Fultz P. N., McClure H. M., Anderson D. C., Switzer W. M. Identification and biologic characterization of an acutely lethal variant of simian immunodeficiency virus from sooty mangabeys (SIV/SMM). AIDS Res Hum Retroviruses. 1989 Aug;5(4):397–409. doi: 10.1089/aid.1989.5.397. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Haase A. T. Pathogenesis of lentivirus infections. Nature. 1986 Jul 10;322(6075):130–136. doi: 10.1038/322130a0. [DOI] [PubMed] [Google Scholar]
  10. Haase A. T., Stowring L., Harris J. D., Traynor B., Ventura P., Peluso R., Brahic M. Visna DNA synthesis and the tempo of infection in vitro. Virology. 1982 Jun;119(2):399–410. doi: 10.1016/0042-6822(82)90099-x. [DOI] [PubMed] [Google Scholar]
  11. Hoover E. A., Mullins J. I., Quackenbush S. L., Gasper P. W. Experimental transmission and pathogenesis of immunodeficiency syndrome in cats. Blood. 1987 Dec;70(6):1880–1892. [PubMed] [Google Scholar]
  12. Keshet E., Temin H. M. Cell killing by spleen necrosis virus is correlated with a transient accumulation of spleen necrosis virus DNA. J Virol. 1979 Aug;31(2):376–388. doi: 10.1128/jvi.31.2.376-388.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Klatzmann D., Barré-Sinoussi F., Nugeyre M. T., Danquet C., Vilmer E., Griscelli C., Brun-Veziret F., Rouzioux C., Gluckman J. C., Chermann J. C. Selective tropism of lymphadenopathy associated virus (LAV) for helper-inducer T lymphocytes. Science. 1984 Jul 6;225(4657):59–63. doi: 10.1126/science.6328660. [DOI] [PubMed] [Google Scholar]
  14. McClure H. M., Anderson D. C., Fultz P. N., Ansari A. A., Lockwood E., Brodie A. Spectrum of disease in macaque monkeys chronically infected with SIV/SMM. Vet Immunol Immunopathol. 1989 May;21(1):13–24. doi: 10.1016/0165-2427(89)90126-8. [DOI] [PubMed] [Google Scholar]
  15. Moss A. R., Bacchetti P. Natural history of HIV infection. AIDS. 1989 Feb;3(2):55–61. doi: 10.1097/00002030-198902000-00001. [DOI] [PubMed] [Google Scholar]
  16. Mullins J. I., Casey J. W., Nicolson M. O., Davidson N. Sequence organization of feline leukemia virus DNA in infected cells. Nucleic Acids Res. 1980 Aug 11;8(15):3287–3305. doi: 10.1093/nar/8.15.3287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Mullins J. I., Hoover E. A., Overbaugh J., Quackenbush S. L., Donahue P. R., Poss M. L. FeLV-FAIDS-induced immunodeficiency syndrome in cats. Vet Immunol Immunopathol. 1989 May;21(1):25–37. doi: 10.1016/0165-2427(89)90127-x. [DOI] [PubMed] [Google Scholar]
  19. Mullins J. I., Hoover E. A., Quackenbush S. L., Donahue P. R. Disease progression and viral genome variants in experimental feline leukemia virus-induced immunodeficiency syndrome. J Acquir Immune Defic Syndr. 1991;4(6):547–557. [PubMed] [Google Scholar]
  20. Newell M. K., Haughn L. J., Maroun C. R., Julius M. H. Death of mature T cells by separate ligation of CD4 and the T-cell receptor for antigen. Nature. 1990 Sep 20;347(6290):286–289. doi: 10.1038/347286a0. [DOI] [PubMed] [Google Scholar]
  21. Overbaugh J., Donahue P. R., Quackenbush S. L., Hoover E. A., Mullins J. I. Molecular cloning of a feline leukemia virus that induces fatal immunodeficiency disease in cats. Science. 1988 Feb 19;239(4842):906–910. doi: 10.1126/science.2893454. [DOI] [PubMed] [Google Scholar]
  22. Pang S., Koyanagi Y., Miles S., Wiley C., Vinters H. V., Chen I. S. High levels of unintegrated HIV-1 DNA in brain tissue of AIDS dementia patients. Nature. 1990 Jan 4;343(6253):85–89. doi: 10.1038/343085a0. [DOI] [PubMed] [Google Scholar]
  23. Pauza C. D., Galindo J. E., Richman D. D. Reinfection results in accumulation of unintegrated viral DNA in cytopathic and persistent human immunodeficiency virus type 1 infection of CEM cells. J Exp Med. 1990 Oct 1;172(4):1035–1042. doi: 10.1084/jem.172.4.1035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Pauza C. D., Galindo J. Persistent human immunodeficiency virus type 1 infection of monoblastoid cells leads to accumulation of self-integrated viral DNA and to production of defective virions. J Virol. 1989 Sep;63(9):3700–3707. doi: 10.1128/jvi.63.9.3700-3707.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Pedersen N. C., Ho E. W., Brown M. L., Yamamoto J. K. Isolation of a T-lymphotropic virus from domestic cats with an immunodeficiency-like syndrome. Science. 1987 Feb 13;235(4790):790–793. doi: 10.1126/science.3643650. [DOI] [PubMed] [Google Scholar]
  26. Perryman L. E., Hoover E. A., Yohn D. S. Immunologic reactivity of the cat: immunosuppression in experimental feline leukemia. J Natl Cancer Inst. 1972 Nov;49(5):1357–1365. [PubMed] [Google Scholar]
  27. Poss M. L., Mullins J. I., Hoover E. A. Posttranslational modifications distinguish the envelope glycoprotein of the immunodeficiency disease-inducing feline leukemia virus retrovirus. J Virol. 1989 Jan;63(1):189–195. doi: 10.1128/jvi.63.1.189-195.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Poss M. L., Quackenbush S. L., Mullins J. I., Hoover E. A. Characterization and significance of delayed processing of the feline leukemia virus FeLV-FAIDS envelope glycoprotein. J Virol. 1990 Sep;64(9):4338–4345. doi: 10.1128/jvi.64.9.4338-4345.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Quackenbush S. L., Donahue P. R., Dean G. A., Myles M. H., Ackley C. D., Cooper M. D., Mullins J. I., Hoover E. A. Lymphocyte subset alterations and viral determinants of immunodeficiency disease induction by the feline leukemia virus FeLV-FAIDS. J Virol. 1990 Nov;64(11):5465–5474. doi: 10.1128/jvi.64.11.5465-5474.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Quackenbush S. L., Mullins J. I., Hoover E. A. Colony forming T lymphocyte deficit in the development of feline retrovirus induced immunodeficiency syndrome. Blood. 1989 Feb;73(2):509–516. [PubMed] [Google Scholar]
  31. Robinson H. L., Miles B. D. Avian leukosis virus-induced osteopetrosis is associated with the persistent synthesis of viral DNA. Virology. 1985 Feb;141(1):130–143. doi: 10.1016/0042-6822(85)90189-8. [DOI] [PubMed] [Google Scholar]
  32. Robinson H. L., Zinkus D. M. Accumulation of human immunodeficiency virus type 1 DNA in T cells: results of multiple infection events. J Virol. 1990 Oct;64(10):4836–4841. doi: 10.1128/jvi.64.10.4836-4841.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Rojko J. L., Kociba G. J., Abkowitz J. L., Hamilton K. L., Hardy W. D., Jr, Ihle J. N., O'Brien S. J. Feline lymphomas: immunological and cytochemical characterization. Cancer Res. 1989 Jan 15;49(2):345–351. [PubMed] [Google Scholar]
  34. Salmon P., Olivier R., Riviere Y., Brisson E., Gluckman J. C., Kieny M. P., Montagnier L., Klatzmann D. Loss of CD4 membrane expression and CD4 mRNA during acute human immunodeficiency virus replication. J Exp Med. 1988 Dec 1;168(6):1953–1969. doi: 10.1084/jem.168.6.1953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Shaw G. M., Hahn B. H., Arya S. K., Groopman J. E., Gallo R. C., Wong-Staal F. Molecular characterization of human T-cell leukemia (lymphotropic) virus type III in the acquired immune deficiency syndrome. Science. 1984 Dec 7;226(4679):1165–1171. doi: 10.1126/science.6095449. [DOI] [PubMed] [Google Scholar]
  36. Shaw G. M., Harper M. E., Hahn B. H., Epstein L. G., Gajdusek D. C., Price R. W., Navia B. A., Petito C. K., O'Hara C. J., Groopman J. E. HTLV-III infection in brains of children and adults with AIDS encephalopathy. Science. 1985 Jan 11;227(4683):177–182. doi: 10.1126/science.2981429. [DOI] [PubMed] [Google Scholar]
  37. Snyder H. W., Jr, Hardy W. D., Jr, Zuckerman E. E., Fleissner E. Characterisation of a tumour-specific antigen on the surface of feline lymphosarcoma cells. Nature. 1978 Oct 19;275(5681):656–658. doi: 10.1038/275656a0. [DOI] [PubMed] [Google Scholar]
  38. Somasundaran M., Robinson H. L. A major mechanism of human immunodeficiency virus-induced cell killing does not involve cell fusion. J Virol. 1987 Oct;61(10):3114–3119. doi: 10.1128/jvi.61.10.3114-3119.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Stevenson M., Meier C., Mann A. M., Chapman N., Wasiak A. Envelope glycoprotein of HIV induces interference and cytolysis resistance in CD4+ cells: mechanism for persistence in AIDS. Cell. 1988 May 6;53(3):483–496. doi: 10.1016/0092-8674(88)90168-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Temin H. M. Mechanisms of cell killing/cytopathic effects by nonhuman retroviruses. Rev Infect Dis. 1988 Mar-Apr;10(2):399–405. doi: 10.1093/clinids/10.2.399. [DOI] [PubMed] [Google Scholar]
  41. Terai C., Kornbluth R. S., Pauza C. D., Richman D. D., Carson D. A. Apoptosis as a mechanism of cell death in cultured T lymphoblasts acutely infected with HIV-1. J Clin Invest. 1991 May;87(5):1710–1715. doi: 10.1172/JCI115188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Weller S. K., Joy A. E., Temin H. M. Correlation between cell killing and massive second-round superinfection by members of some subgroups of avian leukosis virus. J Virol. 1980 Jan;33(1):494–506. doi: 10.1128/jvi.33.1.494-506.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Weller S. K., Temin H. M. Cell killing by avian leukosis viruses. J Virol. 1981 Sep;39(3):713–721. doi: 10.1128/jvi.39.3.713-721.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. de Vries J. E., van Benthem M., Rümke P. Separation of viable from nonviable tumor cells by flotation on a Ficoll-Triosil mixture. Transplantation. 1973 Apr;15(4):409–410. doi: 10.1097/00007890-197304000-00011. [DOI] [PubMed] [Google Scholar]

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