title: Analysis of the disease potential of a recombinant retrovirus containing Friend murine leukemia virus sequences and a unique long terminal repeat from feline leukemia virus.
abstract: We have molecularly cloned a feline leukemia virus (FeLV) (clone 33) from a domestic cat with acute myeloid leukemia (AML). The long terminal repeat (LTR) of this virus, like the LTRs present in FeLV proviruses from other cats with AML, contains an unusual structure in its U3 region upstream of the enhancer (URE) consisting of three tandem direct repeats of 47 bp. To test the disease potential and specificity of this unique FeLV LTR, we replaced the U3 region of the LTR of the erythroleukemia-inducing Friend murine leukemia virus (F-MuLV) with that of FeLV clone 33. When the resulting virus, F33V, was injected into newborn mice, almost all of the mice eventually developed hematopoietic malignancies, with a significant percentage being in the myeloid lineage. This is in contrast to mice injected with an F-MuLV recombinant containing the U3 region of another FeLV that lacks repetitive URE sequences, none of which developed myeloid malignancies. Examination of tumor proviruses from F33V-infected mice failed to detect any changes in FeLV U3 sequences other than that in the URE. Like F-MuLV-infected mice, those infected with the F-MuLV/FeLV recombinants were able to generate and replicate mink cell focus-inducing viruses. Our studies are consistent with the idea that the presence of repetitive sequences upstream of the enhancer in the LTR of FeLV may favor the activation of this promoter in myeloid cells and contribute to the development of malignancies in this hematopoietic lineage.
authors.affiliation: Basic Research Laboratory, National Cancer Institute, Frederick, Maryland 21702-1201, USA.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nishigaki
authors.forename: Charlotte
authors.initials: C
authors.lastname: Hanson
authors.forename: Delores
authors.initials: D
authors.lastname: Thompson
authors.forename: Takashi
authors.initials: T
authors.lastname: Yugawa
authors.forename: Masaharu
authors.initials: M
authors.lastname: Hisasue
authors.forename: Hajime
authors.initials: H
authors.lastname: Tsujimoto
authors.forename: Sandra
authors.initials: S
authors.lastname: Ruscetti
mesh_terms: D000818:Animals; D001483:Base Sequence; D002415:Cats; D002460:Cell Line; D003001:Cloning, Molecular; D004279:DNA, Viral; D005622:Friend murine leukemia virus / Q000235:genetics* / Q000502:physiology; D005256:Leukemia Virus, Feline / Q000235:genetics*; D004915:Leukemia, Erythroblastic, Acute / Q000821:virology; D007942:Leukemia, Experimental / Q000821:virology; D007951:Leukemia, Myeloid / Q000821:virology; D008223:Lymphoma / Q000821:virology; D051379:Mice; D008908:Mink Cell Focus-Inducing Viruses / Q000235:genetics; D008969:Molecular Sequence Data; D011995:Recombination, Genetic; D012190:Retroviridae; D012192:Retroviridae Infections / Q000821:virology; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D020079:Terminal Repeat Sequences; D014412:Tumor Virus Infections / Q000821:virology
chemical_list: D004279:DNA, Viral