Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
Recombination between feline leukemia virus (FeLV) subgroup a and endogenous FeLV-related elements in leukemogenesis.
Diss Abstr Int [B]; 54(4):1840 1993. Unique Identifier : AIDSLINE ICDB/94601687 Sheets RL; Univ. of Southern California
Abstract:
The hypothesis examined herein is that recombination between exogenous infectious FeLVs and endogenous noninfectious FeLV-related elements is involved in leukemogenesis induced by FeLV infection. Thus, I have (1) characterized the molecular structure of recombinants generated and biologically selected in tissue culture and (2) detected the presence of recombinants of similar structure in naturally arising feline lymphosarcomas (LSAs). By coexpressing cloned proviruses of FeLV subgroup A (FeLV-A) and endogenous envelope (env)-containing elements in feline cells, recombinant viruses arose that were isolated by selection for growth in human cells, which are non-permissive for infection by FeLV-A or the noninfectious endogenous elements. By PCR amplification, cloning of the PCR products, and nucleotide sequence determination, the structure of these recombinants was elucidated. They contained as much as three-quarters of the surface glycoprotein (SU), beginning from the amino-terminus, encoded by endogenous sequences before crossing-over to FeLV-A sequences. The cross-over sites identified were contained within a 250 bp region in the middle of the approx 1500 bp SU coding region. Mutations were also identified in several of the recombinants at a pentapeptide epitope representing the major neutralizing determinant for FeLV-A. By utilizing a PCR strategy to discriminate between endogenous, FeLV-A, or recombinant proviruses present in naturally occurring feline LSAs, recombinants of the structure elucidated in vitro were detected in three-quarters of FeLV capsid antigen-positive thymic and alimentary LSAs, but in only one-third of FeLV-positive multicentric LSAs. After cloning of the PCR products and nucleotide sequence determination, four recombinant sequence structural motifs were identified. One motif represents FeLV subgroup B (FeLV-B), shown previously to be a recombinant between FeLV-A and endogenous FeLV. The other motifs show varying amounts of endogenous-like env sequences before crossing-over to FeLV-A sequences. The cross-over sites were detected: (1) within the middle of SU, (2) at the SU/TM (transmembrane protein) boundary, and (3) within the middle of TM. Thus, I have shown, by molecular genetic techniques, that recombinant FeLVs are present in a majority of FeLV-positive LSAs, especially prevalent in thymic and alimentary LSAs. (Copies available exclusively from Micrographics Department, Doheny Library, USC, Los Angeles, CA 90089-0182. Not available from University Microfilms Int'l.)
Keywords: Crossing Over (Genetics) Gene Products, env/GENETICS Leukemia Virus, Feline/*GENETICS Leukemia, Experimental/*GENETICS Lymphoma, Diffuse/*GENETICS Proviruses/GENETICS *Recombination, Genetic Retroviridae Infections/*GENETICS Tumor Virus Infections/*GENETICS THESIS 940630
M9460927
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Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
