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1996-03-09
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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).