Viral genetic determinants of T-cell killing and immunodeficiency disease induction by the feline leukemia virus FeLV-FAIDS.
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.
Donahue
P R
PR
Biomedical Research Institute, Children's Hospital of St. Paul, Minnesota 55102.
Quackenbush
S L
SL
Gallo
M V
MV
deNoronha
C M
CM
Overbaugh
J
J
Hoover
E A
EA
Mullins
J I
JI
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D002415:Cats; D002460:Cell Line; D002470:Cell Survival; D002678:Chimera; D003588:Cytopathogenic Effect, Viral; D004279:DNA, Viral / Q000737:chemistry*; D016181:Feline Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000382:microbiology*; D005256:Leukemia Virus, Feline / Q000235:genetics* / Q000472:pathogenicity; D008969:Molecular Sequence Data; D009154:Mutation; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000166:cytology / Q000382:microbiology*; D014162:Transfection; D014779:Virus Replication
D004279:DNA, Viral