Lymphocytotoxic strains of feline leukemia virus induce apoptosis in feline T4-thymic lymphoma cells

J. L. Rojko, R. M. Fulton, L. J. Rezanka, L. L. Williams, E. Copelan, C. M. Cheney, G. S. Reichel, J. C. Neil, L. E. Mathes, T. G. Fisher, M. W. Cloyd

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Feline leukemia retrovirus (FeLV) strains with subgroup C env genes kill feline T4 lymphoma 3201 cells by 7 to 12 days after in vitro inoculation, whereas FeLV strains with subgroup A env genes do not. Neither FeLV-A nor FeLV-C kill feline fibroblasts. FeLV-C, but not FeLV-A, is replicated to high titer by 3201 cells and productive infection precedes death by 3 to 7 days. Transcriptional activity of the FeLV-C long terminal repeat, as assessed by chloramphenicol acetyltransferase activity, is high in feline lymphoid cells but low in feline fibroblasts. Activity of the FeLV-A long terminal repeat is moderate in both cell types. FeLV-C-infected cells from aggregates 1 to 4 days before dying; ultrastructurally, virus particles can be seen approximating the clustered cells. Dying cells demonstrate nuclear condensation, surface blebbing, and fragmentation. DNA fragmentation and laddering compatible with apoptosis occur 1 to 2 days before massive cell death. In FeLV-C-infected 3201 cells, a shift from phospholipid to neutral lipid incorporation of [14C]oleic acid, increases in palmitic acid proportions and decreases in linoleic acid proportions occur 1 to 2 days before peak killing. Exposure of 3201 cells to ultraviolet-inactivated FeLV- KT (200-800 μg/106 cells) causes cytostasis within 2 days and death within 4 days. Blebbing and nuclear condensation occur but clusters do not form. The induction of programmed cell death in feline thymic lymphoma cells by subgroup C feline retroviruses may be relevant to the pathogenesis of FeLV- induced thymic atrophy, paracortical lymphoid depletion and acquired immunodeficiency in vivo.

Original languageEnglish (US)
Pages (from-to)418-426
Number of pages9
JournalLaboratory Investigation
Volume66
Issue number4
StatePublished - Jan 1 1992

Keywords

  • Cytopathic retroviruses
  • Programmed cell death

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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    Rojko, J. L., Fulton, R. M., Rezanka, L. J., Williams, L. L., Copelan, E., Cheney, C. M., Reichel, G. S., Neil, J. C., Mathes, L. E., Fisher, T. G., & Cloyd, M. W. (1992). Lymphocytotoxic strains of feline leukemia virus induce apoptosis in feline T4-thymic lymphoma cells. Laboratory Investigation, 66(4), 418-426.