Document 0547
 DOCN  M9650547
 TI    Development of a human thymic organ culture model for the study of HIV
       pathogenesis.
 DT    9605
 AU    Bonyhadi ML; Su L; Auten J; McCune JM; Kaneshima H; HIV Group, SyStemix,
       Inc., Palo Alto, California 94304, USA.
 SO    AIDS Res Hum Retroviruses. 1995 Sep;11(9):1073-80. Unique Identifier :
       AIDSLINE MED/96089214
 AB    The development of effective therapies for the treatment of AIDS would
       be facilitated by a better understanding of HIV pathogenesis in vivo.
       While some aspects of pathogenesis may be assessed by standard tissue
       culture assays, in vivo animal models may provide clues to other aspects
       of HIV-mediated progression toward AIDS. Current animal models include
       primate models for the study of simian immunodeficiency virus (SIV) and
       HIV, SCID-hu and hu-PBL SCID mouse models for the study of HIV, and
       feline models for the study of feline immunodeficiency virus (FIV). In
       general these models are costly and labor intensive. We have developed a
       simple human fetal thymic organ culture (TOC) system that is permissive
       for HIV infection and that exhibits pathology similar to that observed
       in vivo. A key feature of this system is the time-dependent destruction
       of thymocytes typified by the preferential loss of CD4-expressing cells.
       HIV-mediated thymocyte destruction occurs by a process involving
       programmed cell death. We have infected TOC with a panel of HIV isolates
       and found that the resulting viral replicative and pathogenic profiles
       are similar to those seen in the SCID-hu Thy/Liv mouse, yet different
       from profiles observed in standard PHA-blast tissue culture assays. In
       addition, we find that TOC may be used to assess efficacy of antiviral
       agents such as AZT (3'-azido-3'-deoxythymidine) and ddI
       (2',3'-dideoxyinosine) in blocking both viral replication and
       virus-induced pathology. These results indicate that this model is
       amenable to the systematic manipulation, analysis, and characterization
       of a variety of HIV virus isolates and antiviral therapies.
 DE    Animal  Antiviral Agents/PHARMACOLOGY  Apoptosis  Cats  Comparative
       Study  CD4-CD8 Ratio  CD4-Positive T-Lymphocytes/IMMUNOLOGY/PATHOLOGY
       Didanosine/PHARMACOLOGY  Drug Screening/METHODS  Fetus  Human  HIV
       Infections/DRUG THERAPY/*ETIOLOGY/IMMUNOLOGY  HIV-1/DRUG
       EFFECTS/PHYSIOLOGY/*PATHOGENICITY  Mice  *Models, Biological  Organ
       Culture/METHODS/STANDARDS  Support, Non-U.S. Gov't  Support, U.S. Gov't,
       P.H.S.  Thymus Gland/IMMUNOLOGY/PATHOLOGY/*VIROLOGY  Time Factors  Virus
       Replication  Zidovudine/PHARMACOLOGY  JOURNAL ARTICLE

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