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. 1993 Oct;67(10):5724–5732. doi: 10.1128/jvi.67.10.5724-5732.1993

Delayed cytopathicity of a feline leukemia virus variant is due to four mutations in the transmembrane protein gene.

E Thomas 1, J Overbaugh 1
PMCID: PMC237989  PMID: 8396654

Abstract

Two molecularly cloned, replication-defective variants of feline leukemia virus, called 61B and 61C, have both been shown to cause fatal immunodeficiency in cats when coinfected with a replication-competent, minimally pathogenic helper virus, but 61B exhibits a longer latency period between infection and disease (J. Overbaugh, E. A. Hoover, J. I. Mullins, D. P. W. Burns, L. Rudensey, S. L. Quackenbush, V. Stallard, and P. R. Donahue, Virology 188:558-569, 1992). Infection of the 3201 feline T-cell line with 61B plus helper virus also results in longer time from infection to cytopathic effect compared with 61C plus helper virus, providing an in vitro system with which to study the mechanism for this difference. We report that the primary determinant of cytopathicity of 61B maps to gp70, the extracellular envelope glycoprotein. The long latency of 61B, on the other hand, maps to the extracellular portion of the envelope transmembrane protein, in which there are only four predicted amino acid differences between 61B and 61C. These differences render 61B replication defective, and two of the predicted amino acid changes lie in a region that is highly conserved among many retroviruses. The eventual onset of 61B cytopathicity in cell culture was associated with the outgrowth of an apparent recombinant virus that encodes the pathogenic gp70 of 61B and replaces the transmembrane protein of 61B with that of the helper virus. Thus, during in vitro infection, a cytopathic virus evolved from a replication-defective virus and a nonpathogenic virus, suggesting that recombination between multiple variants in natural infection may influence progression of feline leukemia virus-associated immunodeficiency disease.

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Selected References

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

  1. Benveniste R. E., Sherr C. J., Todaro G. J. Evolution of type C viral genes: origin of feline leukemia virus. Science. 1975 Nov 28;190(4217):886–888. doi: 10.1126/science.52892. [DOI] [PubMed] [Google Scholar]
  2. Bosch V., Pawlita M. Mutational analysis of the human immunodeficiency virus type 1 env gene product proteolytic cleavage site. J Virol. 1990 May;64(5):2337–2344. doi: 10.1128/jvi.64.5.2337-2344.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bosselman R. A., van Straaten F., Van Beveren C., Verma I. M., Vogt M. Analysis of the env gene of a molecularly cloned and biologically active Moloney mink cell focus-forming proviral DNA. J Virol. 1982 Oct;44(1):19–31. doi: 10.1128/jvi.44.1.19-31.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brody B. A., Hunter E. Mutations within the env gene of Mason-Pfizer monkey virus: effects on protein transport and SU-TM association. J Virol. 1992 Jun;66(6):3466–3475. doi: 10.1128/jvi.66.6.3466-3475.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cianciolo G. J., Copeland T. D., Oroszlan S., Snyderman R. Inhibition of lymphocyte proliferation by a synthetic peptide homologous to retroviral envelope proteins. Science. 1985 Oct 25;230(4724):453–455. doi: 10.1126/science.2996136. [DOI] [PubMed] [Google Scholar]
  6. Cianciolo G. J., Kipnis R. J., Snyderman R. Similarity between p15E of murine and feline leukaemia viruses and p21 of HTLV. Nature. 1984 Oct 11;311(5986):515–515. doi: 10.1038/311515a0. [DOI] [PubMed] [Google Scholar]
  7. Dedera D., Gu R. L., Ratner L. Conserved cysteine residues in the human immunodeficiency virus type 1 transmembrane envelope protein are essential for precursor envelope cleavage. J Virol. 1992 Feb;66(2):1207–1209. doi: 10.1128/jvi.66.2.1207-1209.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Donahue P. R., Quackenbush S. L., Gallo M. V., deNoronha C. M., Overbaugh J., Hoover E. A., Mullins J. I. Viral genetic determinants of T-cell killing and immunodeficiency disease induction by the feline leukemia virus FeLV-FAIDS. J Virol. 1991 Aug;65(8):4461–4469. doi: 10.1128/jvi.65.8.4461-4469.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dong J. Y., Dubay J. W., Perez L. G., Hunter E. Mutations within the proteolytic cleavage site of the Rous sarcoma virus glycoprotein define a requirement for dibasic residues for intracellular cleavage. J Virol. 1992 Feb;66(2):865–874. doi: 10.1128/jvi.66.2.865-874.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Elder J. H., Mullins J. I. Nucleotide sequence of the envelope gene of Gardner-Arnstein feline leukemia virus B reveals unique sequence homologies with a murine mink cell focus-forming virus. J Virol. 1983 Jun;46(3):871–880. doi: 10.1128/jvi.46.3.871-880.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Freed E. O., Risser R. The role of envelope glycoprotein processing in murine leukemia virus infection. J Virol. 1987 Sep;61(9):2852–2856. doi: 10.1128/jvi.61.9.2852-2856.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gallaher W. R., Ball J. M., Garry R. F., Griffin M. C., Montelaro R. C. A general model for the transmembrane proteins of HIV and other retroviruses. AIDS Res Hum Retroviruses. 1989 Aug;5(4):431–440. doi: 10.1089/aid.1989.5.431. [DOI] [PubMed] [Google Scholar]
  14. Guo H. G., Veronese F. M., Tschachler E., Pal R., Kalyanaraman V. S., Gallo R. C., Reitz M. S., Jr Characterization of an HIV-1 point mutant blocked in envelope glycoprotein cleavage. Virology. 1990 Jan;174(1):217–224. doi: 10.1016/0042-6822(90)90070-8. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Hunter E., Swanstrom R. Retrovirus envelope glycoproteins. Curr Top Microbiol Immunol. 1990;157:187–253. doi: 10.1007/978-3-642-75218-6_7. [DOI] [PubMed] [Google Scholar]
  17. Katz R. A., Skalka A. M. Generation of diversity in retroviruses. Annu Rev Genet. 1990;24:409–445. doi: 10.1146/annurev.ge.24.120190.002205. [DOI] [PubMed] [Google Scholar]
  18. Koch W., Hunsmann G., Friedrich R. Nucleotide sequence of the envelope gene of Friend murine leukemia virus. J Virol. 1983 Jan;45(1):1–9. doi: 10.1128/jvi.45.1.1-9.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kumar D. V., Berry B. T., Roy-Burman P. Nucleotide sequence and distinctive characteristics of the env gene of endogenous feline leukemia provirus. J Virol. 1989 May;63(5):2379–2384. doi: 10.1128/jvi.63.5.2379-2384.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lenz J., Crowther R., Straceski A., Haseltine W. Nucleotide sequence of the Akv env gene. J Virol. 1982 May;42(2):519–529. doi: 10.1128/jvi.42.2.519-529.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Linial M., Fenno J., Burnette W. N., Rohrschneider L. Synthesis and processing of viral glycoproteins in two nonconditional mutants of Rous sarcoma virus. J Virol. 1980 Oct;36(1):280–290. doi: 10.1128/jvi.36.1.280-290.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. McCune J. M., Rabin L. B., Feinberg M. B., Lieberman M., Kosek J. C., Reyes G. R., Weissman I. L. Endoproteolytic cleavage of gp160 is required for the activation of human immunodeficiency virus. Cell. 1988 Apr 8;53(1):55–67. doi: 10.1016/0092-8674(88)90487-4. [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. 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]
  25. Overbaugh J., Hoover E. A., Mullins J. I., Burns D. P., Rudensey L., Quackenbush S. L., Stallard V., Donahue P. R. Structure and pathogenicity of individual variants within an immunodeficiency disease-inducing isolate of FeLV. Virology. 1992 Jun;188(2):558–569. doi: 10.1016/0042-6822(92)90510-v. [DOI] [PubMed] [Google Scholar]
  26. Overbaugh J., Riedel N., Hoover E. A., Mullins J. I. Transduction of endogenous envelope genes by feline leukaemia virus in vitro. Nature. 1988 Apr 21;332(6166):731–734. doi: 10.1038/332731a0. [DOI] [PubMed] [Google Scholar]
  27. Patarca R., Haseltine W. A. Similarities among retrovirus proteins. Nature. 1984 Dec 6;312(5994):496–496. doi: 10.1038/312496a0. [DOI] [PubMed] [Google Scholar]
  28. Perez L. G., Hunter E. Mutations within the proteolytic cleavage site of the Rous sarcoma virus glycoprotein that block processing to gp85 and gp37. J Virol. 1987 May;61(5):1609–1614. doi: 10.1128/jvi.61.5.1609-1614.1987. [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. Riedel N., Hoover E. A., Dornsife R. E., Mullins J. I. Pathogenic and host range determinants of the feline aplastic anemia retrovirus. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2758–2762. doi: 10.1073/pnas.85.8.2758. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Riedel N., Hoover E. A., Gasper P. W., Nicolson M. O., Mullins J. I. Molecular analysis and pathogenesis of the feline aplastic anemia retrovirus, feline leukemia virus C-Sarma. J Virol. 1986 Oct;60(1):242–250. doi: 10.1128/jvi.60.1.242-250.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Seiki M., Hattori S., Hirayama Y., Yoshida M. Human adult T-cell leukemia virus: complete nucleotide sequence of the provirus genome integrated in leukemia cell DNA. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3618–3622. doi: 10.1073/pnas.80.12.3618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Shinnick T. M., Lerner R. A., Sutcliffe J. G. Nucleotide sequence of Moloney murine leukaemia virus. Nature. 1981 Oct 15;293(5833):543–548. doi: 10.1038/293543a0. [DOI] [PubMed] [Google Scholar]
  35. 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]
  36. Sodroski J., Patarca R., Perkins D., Briggs D., Lee T. H., Essex M., Coligan J., Wong-Staal F., Gallo R. C., Haseltine W. A. Sequence of the envelope glycoprotein gene of type II human T lymphotropic virus. Science. 1984 Jul 27;225(4660):421–424. doi: 10.1126/science.6204380. [DOI] [PubMed] [Google Scholar]
  37. Sonigo P., Barker C., Hunter E., Wain-Hobson S. Nucleotide sequence of Mason-Pfizer monkey virus: an immunosuppressive D-type retrovirus. Cell. 1986 May 9;45(3):375–385. doi: 10.1016/0092-8674(86)90323-5. [DOI] [PubMed] [Google Scholar]
  38. Syu W. J., Lee W. R., Du B., Yu Q. C., Essex M., Lee T. H. Role of conserved gp41 cysteine residues in the processing of human immunodeficiency virus envelope precursor and viral infectivity. J Virol. 1991 Nov;65(11):6349–6352. doi: 10.1128/jvi.65.11.6349-6352.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. 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]
  40. Wain-Hobson S., Sonigo P., Danos O., Cole S., Alizon M. Nucleotide sequence of the AIDS virus, LAV. Cell. 1985 Jan;40(1):9–17. doi: 10.1016/0092-8674(85)90303-4. [DOI] [PubMed] [Google Scholar]

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