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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).