Document 0328
 DOCN  M9650328
 TI    Autocrine interferon-beta synthesis for gene therapy of HIV infection:
       increased resistance to HIV-1 in lymphocytes from healthy and
       HIV-infected individuals.
 DT    9605
 AU    Vieillard V; Lauret E; Maguer V; Jacomet C; Rozenbaum W; Gazzolo L; De
       Maeyer E; URA 1343 Centre National de la Recherche Scientifique,
       Institut; Curie, University of Paris 11, Orsay, France.
 SO    AIDS. 1995 Nov;9(11):1221-8. Unique Identifier : AIDSLINE MED/96126175
 AB    OBJECTIVE: To explore the possibility of gene therapy of HIV infection
       based on the multiple antiretroviral activities of interferon
       (IFN)-beta. DESIGN: We introduced into HIV target cells an IFN-beta gene
       placed under an expression control ensuring a low and constitutive
       expression, sufficient to confer a permanent antiviral state without
       impeding normal cell function. METHODS: We transformed, with an efficacy
       ranging from 20-55%, peripheral blood lymphocytes (PBL) derived from
       healthy, seronegative donors, and from asymptomatic HIV-infected
       individuals by the HMB-KbHuIFN beta retroviral vector carrying the human
       IFN-beta coding sequence driven by a fragment of the murine H-2Kb gene
       promoter. RESULTS: The replication rate of the IFN-beta-expressing cells
       was no different from that of untransformed controls during the 21-day
       period of in vitro observation. When IFN-beta-transformed, purified CD4+
       lymphocytes from healthy donors were HIV-1LAI-infected, virus
       replication was inhibited and most of the cells survived, in contrast to
       untransformed CD4+ cells which were all destroyed 12 days after
       infection. Protection of CD4+ cells from the same donors was also
       observed in suspensions of IFN-beta-transformed total PBL that were
       infected with HIV-1LAI. In IFN-beta-transformed PBL from four
       HIV-infected donors, endogenous HIV replication was decreased and 28-69%
       of the CD4+ cells survived at the end of the 21 days in culture. In the
       untransformed control PBL suspensions, all CD4+ cells were destroyed. In
       long-term experiments, HIV-infected, IFN-beta-transformed cell
       populations of the lymphocytic CEM and the promonocytic U937 line were
       kept in culture for 60 days, during which time they remained resistant
       to HIV infection. CONCLUSION: These results indicate that further
       exploration of autocrine IFN-beta production for somatic cell gene
       therapy of HIV infection is warranted.
 DE    Antiviral Agents/*THERAPEUTIC USE  Base Sequence  Cell Line, Transformed
       Cells, Cultured  Gene Therapy  Gene Transfer  Human  HIV
       Infections/METABOLISM/PATHOLOGY/*THERAPY  HIV-1/*DRUG EFFECTS/ISOLATION
       & PURIF  Interferon-beta/BIOSYNTHESIS/GENETICS/*THERAPEUTIC USE
       Lymphocytes/METABOLISM/*VIROLOGY  Molecular Sequence Data  Support,
       Non-U.S. Gov't  JOURNAL ARTICLE

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