Structure and pathogenicity of individual variants within an immunodeficiency disease-inducing isolate of FeLV.
We previously described the molecular cloning of a replication-defective variant of feline leukemia virus (FeLV) that induced fatal immunodeficiency in cats. Eighteen proviruses have now been molecularly cloned from cats inoculated with the original isolate (FeLV-FAIDS) or its in vivo passages. Three were replication-competent and each of these was noncytopathic for the feline T-cell line, 3201. Replication of the prototype, FeLV-61E, in cats was associated with development of T cell tumors in some cats. The remaining 15 proviruses were replication-defective, but each of six of these tested was found to be cytopathic for 3201 cells when rescued with the noncytopathic helper virus, 61E. Three defective/helper virus mixtures were inoculated into cats and all induced fatal immunodeficiency, but with varied efficiency and kinetics. Each of these virus mixtures was attenuated relative to a mixture containing 61E and the intestine-targeted, FeLV-FAIDS-61C prototype defective molecular clone. Furthermore, one replication-competent virus chimera generated using the envelope and LTR of the defective pathogenic variant was incapable of inducing viremia in cats. The observed differences in the biological activity between the defective viruses could be attributed to no more than 10 scattered amino acid changes in envelope and either one or two nucleotide changes in the LTR.
Overbaugh
J
J
Department of Microbiology, University of Washington, Seattle 98195.
Hoover
E A
EA
Mullins
J I
JI
Burns
D P
DP
Rudensey
L
L
Quackenbush
S L
SL
Stallard
V
V
Donahue
P R
PR
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002371:Cat Diseases / Q000382:microbiology; D002415:Cats; D003001:Cloning, Molecular; D003588:Cytopathogenic Effect, Viral; D004279:DNA, Viral / Q000235:genetics; D003673:Defective Viruses / Q000235:genetics; D016181:Feline Acquired Immunodeficiency Syndrome / Q000382:microbiology*; D005256:Leukemia Virus, Feline / Q000235:genetics / Q000472:pathogenicity*; D008969:Molecular Sequence Data; D015183:Restriction Mapping; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D014779:Virus Replication
D004279:DNA, Viral