       Document 0314
 DOCN  M9590314
 TI    A hu-PBL-SCID model to study HIV pathogenesis & therapy.
 DT    9509
 AU    Boyle MJ; Flanigan ME; Ford H Jr; Baseler M; Adelsberger J; Davey RT Jr;
       Lane CH; Laboratory of Medicinal Chemistry, NCI, N PRI/Dyncorp,
       Frederick,; MD, USA.
 SO    Annu Conf Australas Soc HIV Med. 1994 Nov 3-6;6:189 (unnumbered
       abstract). Unique Identifier : AIDSLINE ASHM6/95291785
 AB    PBL from HIV infected patients were engrafted into CB-17 SCID mice to
       develop a novel small animal model for the study of HIV pathogenesis and
       therapy. Engraftment was achieved in 84% of mice, with human
       immunoglobulin (hu-lg) levels and total human mononuclear cell recovery
       by peritoneal wash (PW) similar to control hu-PBL-SCID mice engrafted
       with uninfected donor cells. The hu-lg produced by hu-HIV/PBL-SCID mice
       had broad reactivity against HIV. Virus could be detected in 98% of mice
       by PCR and/or viral co-culture. Relative to human CD4+ cell recovery by
       PW in control hu-PBL-SCID mice (CD4% = 19 +/- 2; n = 40) severe CD4+
       lymphocyte depletion (CD4% = 5 +/- 0.5%; N = 59; p < 0.001) was observed
       in untreated hu-HIV/PBL-SCID mice 18-25 days after engraftment.
       Treatment with FddA, a nucleoside analogue, significantly reduced CD4+
       cell depletion (CD4% = 13 +/- 1; N = 59; p < 0.001) and the frequency of
       virus isolation (70%; p = 0.015) in the hu-HIV/PBL-SCID model. Boosting
       hu-lg levels in the mice by injection of purified donor lg did not
       effect the frequency of CD4+ lymphocyte recovery or virus isolation. The
       administration of a monoclonal antibody to TNF at 10mg/kg significantly
       increased the CD4+ lymphocyte percentage in PW cells (p = 0.04),
       although higher doses were less effective. These studies demonstrate
       that PBL from HIV infected donors can engraft SCID mice,; that HIV can
       be isolated from the splenic and peritoneal tissues of these mice; that
       HIV infection within the model results in rapid CD4+ cell depletion; and
       that antiretroviral therapy is effective in improving CD4+ cell recovery
       and in reducing the frequency of virus isolation.
 DE    Animal  Antiviral Agents/THERAPEUTIC USE  CD4 Lymphocyte Count/DRUG
       EFFECTS  *Disease Models, Animal  Human  HIV Infections/DRUG
       THERAPY/*IMMUNOLOGY/VIROLOGY  Mice  Mice, SCID
       T-Lymphocytes/IMMUNOLOGY/TRANSPLANTATION/*VIROLOGY  Virus Cultivation
       MEETING ABSTRACT

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

