Document 0205
 DOCN  M9460205
 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).