Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1991 Dec;65(12):6495–6508. doi: 10.1128/jvi.65.12.6495-6508.1991

Recombination between feline leukemia virus subgroup B or C and endogenous env elements alters the in vitro biological activities of the viruses.

R Pandey 1, A K Ghosh 1, D V Kumar 1, B A Bachman 1, D Shibata 1, P Roy-Burman 1
PMCID: PMC250696  PMID: 1658356

Abstract

An important question in feline leukemia virus (FeLV) pathogenesis is whether, as in murine leukemia virus infection, homologous recombination between the infecting FeLV and the noninfectious endogenous FeLV-like proviruses serves as a significant base for the generation of proximal pathogens. To begin an analysis of this issue, several recombinant FeLVs were produced by using two different approaches: (i) the regions of the viral envelope (env) gene of a cloned FeLV (subgroup B virus [FeLV-B], Gardner-Arnstein strain) and those of two different endogenous proviral loci were exchanged to create specific FeLV chimeras, and (ii) vectors containing endogenous env and molecularly cloned infectious FeLV-C (Sarma strain) DNA sequences were coexpressed by transfection in nonfeline cells to facilitate recombination. The results of these combined approaches showed that up to three-fourths of the envelope glycoprotein (gp70), beginning from the N-terminal end, could be replaced by endogenous FeLV sequences to produce biologically active chimeric FeLVs. The in vitro replication efficiency or cell tropism of the recombinants appeared to be influenced by the amount of gp70 sequences replaced by the endogenous partner as well as by the locus of origin of the endogenous sequences. Additionally, a characteristic biological effect, aggregation of feline T-lymphoma cells (3201B cell line), was found to be specifically induced by replicating FeLV-C or FeLV-C-based recombinants. Multiple crossover sites in the gp70 protein selected under the conditions used for coexpression were identified. The results of induced coexpression were also supported by rapid generation of FeLV recombinants when FeLV-C was used to infect the feline 3201B cell line that constitutively expresses high levels of endogenous FeLV-specific mRNAs. Furthermore, a large, highly conserved open reading frame in the pol gene of an endogenous FeLV provirus was identified. This observation, particularly in reference to our earlier finding of extensive mutations in the gag gene, reveals a target area for potentially productive homologous recombination upstream of the functional endogenous env gene.

Full text

PDF
6495

Images in this article

6499Image
on p.6499
6500Image
on p.6500
6500Image
on p.6500
6503Image
on p.6503

Selected References

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

  1. Baluda M. A., Roy-Burman P. Partial characterization of RD114 virus by DNA-RNA hybridization studies. Nat New Biol. 1973 Jul 11;244(132):59–62. doi: 10.1038/newbio244059a0. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Berry B. T., Ghosh A. K., Kumar D. V., Spodick D. A., Roy-Burman P. Structure and function of endogenous feline leukemia virus long terminal repeats and adjoining regions. J Virol. 1988 Oct;62(10):3631–3641. doi: 10.1128/jvi.62.10.3631-3641.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Busch M. P., Devi B. G., Soe L. H., Perbal B., Baluda M. A., Roy-Burman P. Characterization of the expression of cellular retrovirus genes and oncogenes in feline cells. Hematol Oncol. 1983 Jan-Mar;1(1):61–75. doi: 10.1002/hon.2900010108. [DOI] [PubMed] [Google Scholar]
  5. Casey J. W., Roach A., Mullins J. I., Burck K. B., Nicolson M. O., Gardner M. B., Davidson N. The U3 portion of feline leukemia virus DNA identifies horizontally acquired proviruses in leukemic cats. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7778–7782. doi: 10.1073/pnas.78.12.7778. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chen E. Y., Seeburg P. H. Supercoil sequencing: a fast and simple method for sequencing plasmid DNA. DNA. 1985 Apr;4(2):165–170. doi: 10.1089/dna.1985.4.165. [DOI] [PubMed] [Google Scholar]
  7. Dale R. M., McClure B. A., Houchins J. P. A rapid single-stranded cloning strategy for producing a sequential series of overlapping clones for use in DNA sequencing: application to sequencing the corn mitochondrial 18 S rDNA. Plasmid. 1985 Jan;13(1):31–40. doi: 10.1016/0147-619x(85)90053-8. [DOI] [PubMed] [Google Scholar]
  8. Davis B. R., Brightman B. K., Chandy K. G., Fan H. Characterization of a preleukemic state induced by Moloney murine leukemia virus: evidence for two infection events during leukemogenesis. Proc Natl Acad Sci U S A. 1987 Jul;84(14):4875–4879. doi: 10.1073/pnas.84.14.4875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Elder J. H., Gautsch J. W., Jensen F. C., Lerner R. A., Hartley J. W., Rowe W. P. Biochemical evidence that MCF murine leukemia viruses are envelope (env) gene recombinants. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4676–4680. doi: 10.1073/pnas.74.10.4676. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ghosh A. K., Roy-Burman P. Characterization of enhancer elements and their mutations in the long terminal repeat of feline endogenous RD-114 proviruses. J Virol. 1989 Oct;63(10):4234–4241. doi: 10.1128/jvi.63.10.4234-4241.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hartley J. W., Wolford N. K., Old L. J., Rowe W. P. A new class of murine leukemia virus associated with development of spontaneous lymphomas. Proc Natl Acad Sci U S A. 1977 Feb;74(2):789–792. doi: 10.1073/pnas.74.2.789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hu W. S., Temin H. M. Retroviral recombination and reverse transcription. Science. 1990 Nov 30;250(4985):1227–1233. doi: 10.1126/science.1700865. [DOI] [PubMed] [Google Scholar]
  14. Jarrett O., Hardy W. D., Jr, Golder M. C., Hay D. The frequency of occurrence of feline leukaemia virus subgroups in cats. Int J Cancer. 1978 Mar 15;21(3):334–337. doi: 10.1002/ijc.2910210314. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Li Q. X., Fan H. Combined infection by Moloney murine leukemia virus and a mink cell focus-forming virus recombinant induces cytopathic effects in fibroblasts or in long-term bone marrow cultures from preleukemic mice. J Virol. 1990 Aug;64(8):3701–3711. doi: 10.1128/jvi.64.8.3701-3711.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Neil J. C., Forrest D., Doggett D. L., Mullins J. I. The role of feline leukaemia virus in naturally occurring leukaemias. Cancer Surv. 1987;6(1):117–137. [PubMed] [Google Scholar]
  18. Niman H. L., Akhavi M., Gardner M. B., Stephenson J. R., Roy-Burman P. Differential expression of two distinct endogenous retrovisus genomes in developing tissues of the domestic cat. J Natl Cancer Inst. 1980 Mar;64(3):587–594. [PubMed] [Google Scholar]
  19. Niman H. L., Stephenson J. R., Gardner M. B., Roy-Burman P. RD-114 and feline leukaemia virus genome expression in natural lymphomas of domestic cats. Nature. 1977 Mar 24;266(5600):357–360. doi: 10.1038/266357a0. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Parimoo S., Bachman B. A., Kumar D., Nichols P. W., Wallace R. B., Roy-Burman P. Analysis of somatic changes in human tumor DNA using synthetic oligonucleotide probes. Cancer Commun. 1989;1(5):293–299. doi: 10.3727/095535489820874832. [DOI] [PubMed] [Google Scholar]
  22. Quintrell N., Varmus H. E., Bishop J. M., Nicholson M. O., McAllister R. M. Homologies among the nucleotide sequences of the genomes of C-type viruses. Virology. 1974 Apr;58(2):568–575. doi: 10.1016/0042-6822(74)90090-7. [DOI] [PubMed] [Google Scholar]
  23. Rein A., Schultz A. Different recombinant murine leukemia viruses use different cell surface receptors. Virology. 1984 Jul 15;136(1):144–152. doi: 10.1016/0042-6822(84)90255-1. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. 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]
  26. Roy-Burman P., Dougherty M., Pal B. K., Charman H. P., Klement V., Gardner M. B. Assay for type C virus in mouse sera based on particulate reverse transcriptase activity. J Virol. 1976 Sep;19(3):1107–1110. doi: 10.1128/jvi.19.3.1107-1110.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  28. Sanger F., Coulson A. R., Barrell B. G., Smith A. J., Roe B. A. Cloning in single-stranded bacteriophage as an aid to rapid DNA sequencing. J Mol Biol. 1980 Oct 25;143(2):161–178. doi: 10.1016/0022-2836(80)90196-5. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Soe L. H., Devi B. G., Mullins J. I., Roy-Burman P. Molecular cloning and characterization of endogenous feline leukemia virus sequences from a cat genomic library. J Virol. 1983 Jun;46(3):829–840. doi: 10.1128/jvi.46.3.829-840.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Soe L. H., Shimizu R. W., Landolph J. R., Roy-Burman P. Molecular analysis of several classes of endogenous feline leukemia virus elements. J Virol. 1985 Dec;56(3):701–710. doi: 10.1128/jvi.56.3.701-710.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Stoye J. P., Moroni C., Coffin J. M. Virological events leading to spontaneous AKR thymomas. J Virol. 1991 Mar;65(3):1273–1285. doi: 10.1128/jvi.65.3.1273-1285.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES