Molecular cloning and characterization of a defective recombinant feline leukaemia virus associated with myeloid leukaemia.
The GM1 strain of feline leukaemia virus (FeLV) was isolated from a naturally occurring case of myeloid leukaemia and induces severe haematopoietic abnormalities, including myeloblastic leukaemia, on inoculation into cats. Molecular clones of FeLV-GM1 proviruses were obtained and studied by restriction enzyme mapping, blot hybridization and partial DNA sequence analysis. Two types of clone were isolated; the first was a replication-competent FeLV of subgroup A, resembling other low or minimally pathogenic FeLV-A isolates; the second was replication-defective with extensive deletions and mutations in gag and pol, although it has an intact env gene of subgroup B phenotype. Large segments of the defective proviruses, from the 5' leader sequence upstream of the gag gene to the 5' half of the env gene, show structural hallmarks of endogenous FeLV-related proviruses. Infectious FeLV-GM1 viruses recovered after transfection were tested for their leukaemogenic potential in newborn cats. Early polyclonal myeloproliferative changes were observed in cats inoculated with FeLV-A/GM1 alone, although these were more pronounced in animals receiving the full FeLV-AB/GM1 complex reconstituted by cotransfection of the defective virus FeLV-B with its FeLV-A helper. Analysis of viruses in the bone marrow showed that replication of the subgroup B component is delayed and restricted to a proportion of cats. Most of the infected cats developed persistent abnormalities of haematopoiesis and one progressed to disseminated myeloid leukaemia. The defective recombinant FeLV-B/GM1 appears to play an indirect but important role in myeloid leukaemogenesis.
Tzavaras
T
T
Beatson Institute for Cancer Research, Bearsden, Glasgow, U.K.
Stewart
M
M
McDougall
A
A
Fulton
R
R
Testa
N
N
Onions
D E
DE
Neil
J C
JC
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D002371:Cat Diseases / Q000382:microbiology*; D002415:Cats; D003001:Cloning, Molecular; D004261:DNA Replication; D004279:DNA, Viral / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D003673:Defective Viruses / Q000235:genetics* / Q000502:physiology; D015750:Genes, gag; D005256:Leukemia Virus, Feline / Q000235:genetics* / Q000502:physiology; D007951:Leukemia, Myeloid / Q000382:microbiology / Q000662:veterinary*; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D011533:Proviruses / Q000235:genetics* / Q000502:physiology; D015183:Restriction Mapping; D014162:Transfection; D014779:Virus Replication
D004279:DNA, Viral