       Document 0412
 DOCN  M9620412
 TI    A nonproducer, interfering human immunodeficiency virus (HIV) type 1
       provirus can be transduced through a murine leukemia virus-based
       retroviral vector: recovery of an anti-HIV mouse/human pseudotype
       retrovirus.
 DT    9602
 AU    Federico M; Nappi F; Ferrari G; Chelucci C; Mavilio F; Verani P;
       Laboratory of Virology, Istituto Superiore di Sanita, Rome,; Italy.
 SO    J Virol. 1995 Nov;69(11):6618-26. Unique Identifier : AIDSLINE
       MED/96013753
 AB    The expression of a human immunodeficiency virus (HIV) type 1 provirus
       (F12-HIV) cloned from a nonproducer, chronically infected CD4
       down-regulated Hut-78 cell clone (F12) does not lead to the formation of
       viral particles and, upon transfection in HeLa CD4+ cells, confers
       resistance to HIV superinfection without affecting the CD4 receptor
       exposure. In an attempt to transfer the anti-HIV properties of F12-HIV
       into human primary cell, we constructed a Moloney murine leukemia
       virus-based retroviral vector containing an F12-HIV genome lacking the
       3' long terminal repeat and part of the nef gene, which was expressed
       under the control of its 5' long terminal repeat. The F12-HIV genome was
       inserted in the orientation opposite to that of the murine leukemia
       virus transcriptional unit and was designated the N2/F12-HIV
       nef-antisense vector. Lymphoblastoid CEMss cells, as well as human
       peripheral blood lymphocytes, were successfully transduced by the
       recombinant retrovirus emerging from the producer PA317 clones. CEMss
       clones expressing the F12-HIV nef-antisense vector became resistant to
       HIV superinfection even at the highest utilized multiplicity of
       infection (10(5) 50% tissue culture infective doses per 10(6) cells). In
       transduced CEMss cells the viral interference induced by the F12-HIV
       expression is not due to CD4 HIV receptor down-regulation. Nonproducer,
       interfering HIV proviruses transduced into retroviral vectors may,
       therefore, provide an alternative strategy for the protection of CD4+
       human primary cells from HIV infection, which strategy may be used in
       designating a safe and efficient gene therapy protocol for patients with
       AIDS.
 DE    Animal  Antigens, CD4  Blotting, Southern  Cell Line  Crosses, Genetic
       Defective Viruses/*GENETICS  DNA, Viral/ANALYSIS  Flow Cytometry  Genes,
       nef  Genetic Vectors  Hela Cells  Human  HIV-1/*GENETICS  *Leukemia
       Viruses, Murine  Lymphocytes/IMMUNOLOGY/*VIROLOGY  Mice
       Proviruses/*GENETICS  Restriction Mapping  Support, Non-U.S. Gov't
       Transfection  Tumor Cells, Cultured  3T3 Cells  JOURNAL ARTICLE

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

