Document 0972
 DOCN  M9460972
 TI    Recombination between feline leukemia virus (FeLV) subgroup a and
       endogenous FeLV-related elements in leukemogenesis.
 DT    9406
 AU    Sheets RL; Univ. of Southern California
 SO    Diss Abstr Int [B]; 54(4):1840 1993. Unique Identifier : AIDSLINE
       ICDB/94601687
 AB    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.)
 DE    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

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).