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M9460586.TXT
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1994-06-25
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Document 0586
DOCN M9460586
TI Development of transgenic sheep that express the visna virus envelope
gene.
DT 9408
AU Clements JE; Wall RJ; Narayan O; Hauer D; Schoborg R; Sheffer D; Powell
A; Carruth LM; Zink MC; Rexroad CE; Johns Hopkins University School of
Medicine, Department of; Comparative Medicine, Baltimore, Maryland
21205.
SO Virology. 1994 May 1;200(2):370-80. Unique Identifier : AIDSLINE
MED/94233701
AB The ovine lentiviruses cause encephalitis, pneumonia, and arthritis in
sheep worldwide. Visna virus is a prototype of this family and the
pathogenesis and molecular biology of the virus has been well
characterized. The envelope proteins of visna virus are responsible for
binding of virus to host cells and for causing cell fusion. The surface
glycoprotein also elicits cellular and humoral immune responses to the
virus, the former being thought to be responsible for eliminating
infected cells as well as causing inflammatory lesions. In this study,
transgenic sheep were constructed that expressed the envelope genes of
visna virus under the control of the visna LTR to investigate the role
of the env gene in the pathogenesis of lentiviral disease in its natural
host. Three transgenic lambs were identified that contain the env
transgene and express the envelope glycoproteins. These transgenic
animals have remained healthy and expression of the viral gene has had
no obvious deleterious effect. Expression of the visna envelope protein
was demonstrated by cell fusion mediated by the envelope gene as well as
by immunoprecipitation of the envelope proteins with monoclonal
antibodies and immunofluorescence analyses of Env protein in cells. The
target cell for visna virus replication in infected animals is the
monocyte/macrophage. In natural infection, the level of viral gene
expression in these cells increases with cell maturation. In the
transgenic sheep, monocytes did not express the envelope glycoproteins
until they differentiated into macrophages in vitro. Expression of the
env mRNA in macrophages was quantitated by an RNase protection assay. In
addition to expression in macrophages, the transgene was expressed by
fibroblasts isolated from skin of the transgenic sheep. Expression of
both the Env and Rev proteins was detected by immunoprecipitation and
immunofluorescence. Two of the three lambs responded immunologically to
the expression of the transgene by producing binding antibodies to the
envelope glycoproteins. Thus, these transgenic sheep provide a model to
study whether a lentivirus glycoprotein will prevent infection or
modulate disease in its natural host after virus challenge.
DE Animal Animals, Transgenic/*GENETICS/IMMUNOLOGY Antibodies,
Viral/BIOSYNTHESIS Cell Fusion Cells, Cultured
Fibroblasts/CYTOLOGY/PHYSIOLOGY Gene Expression Genes, env/*GENETICS
Macrophages/CYTOLOGY/PHYSIOLOGY Recombinant Proteins/BIOSYNTHESIS
Repetitive Sequences, Nucleic Acid/GENETICS Ribonucleases/METABOLISM
RNA, Messenger/METABOLISM Sheep/*GENETICS/IMMUNOLOGY Support, U.S.
Gov't, P.H.S. Tissue Distribution Viral Envelope
Proteins/*BIOSYNTHESIS/IMMUNOLOGY Visna/ETIOLOGY/IMMUNOLOGY/PREVENTION
& CONTROL Visna-Maedi Virus/*GENETICS/IMMUNOLOGY JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).