Lymphocytotoxic strains of feline leukemia virus induce apoptosis in feline T4-thymic lymphoma cells.
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 higher 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 form 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 micrograms/10(6) 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.
Department of Veterinary Pathobiology, Ohio State University, Columbus.
J L
JL
Rojko
R M
RM
Fulton
L J
LJ
Rezanka
L L
LL
Williams
E
E
Copelan
C M
CM
Cheney
G S
GS
Reichel
J C
JC
Neil
L E
LE
Mathes
T G
TG
Fisher
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000382:microbiology / Q000473:pathology*; D002415:Cats; D002453:Cell Cycle; D016923:Cell Death; D004249:DNA Damage; D005347:Fibroblasts / Q000166:cytology; D015752:Genes, env; D014644:Genetic Variation; D005256:Leukemia Virus, Feline / Q000472:pathogenicity* / Q000528:radiation effects; D016582:Leukemia, Feline / Q000473:pathology*; D050356:Lipid Metabolism; D008223:Lymphoma / Q000473:pathology; D009374:Neoplasms, Experimental / Q000473:pathology; D013950:Thymus Gland / Q000473:pathology; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays / Q000009:adverse effects; D014779:Virus Replication