Document 0735
 DOCN  M95A0735
 TI    Reduced provirus burden and enhanced humoral immune function in
       AZT-treated SCID-feline mice inoculated with feline immunodeficiency
       virus.
 DT    9510
 AU    Johnson CM; Selleseth DW; Ellis MN; Childers TA; Tompkins MB; Tompkins
       WA; Department of Microbiology, Pathology, College of Veterinary;
       Medicine, North Carolina State University, Raleigh 27606, USA.
 SO    Vet Immunol Immunopathol. 1995 May;46(1-2):169-80. Unique Identifier :
       AIDSLINE MED/95343526
 AB    The lack of a safe, economical murine lentivirus model for human
       immunodeficiency virus type 1 (HIV-1) infection of humans has hampered
       the preclinical evaluation of potential antiviral compounds, vaccines,
       and biological response modifiers. A small animal model that does not
       employ HIV-1 is needed to minimize risk of accidental human exposure,
       enhance efficient use of scarce experimental compounds, and reduce
       laboratory space necessary to conduct statistically significant in vivo
       trials. Feline immunodeficiency virus (FIV), an immunosuppressive
       lentivirus of domestic cats, has been used extensively as an animal
       model for the pathogenesis and therapy of human HIV-1 infection. Cats,
       however, are not amenable to large-scale efficacy trials because of
       their relatively large size, high cost, and limited degree of
       physiologic characterization, particularly with regard to drug
       metabolism. To adapt the feline immune system to a small laboratory
       animal host, severe combined immunodeficient mice (SCID mice) were
       engrafted with feline lymphoid tissues (forming the SCID-fe mouse) and
       inoculated with FIV. Two quantitative parameters, the incidence of
       provirus detection in feline tissue grafts and the level of feline IgG
       in plasma, were used to demonstrate the antiviral efficacy of
       3'-azido-3'-deoxythymidine (AZT, azidothymidine, Retrovir, zidovudine)
       in the SCID-fe system. Of 17 SCID-fe mice inoculated with 7 x 10(6)
       peripheral blood mononuclear cells (PBMC) from an FIV-infected cat,
       eight had detectable FIV provirus in both the feline thymus and feline
       lymph node implants, as measured by polymerase chain reaction
       (PCR)/Southern blot analysis. Treatment of these mice with AZT at a dose
       of 125 mg kg-1 day-1 in drinking water beginning 1 day prior to FIV
       inoculation and continuing throughout the study interval prevented the
       dual detection of provirus in feline lymph node and thymus grafts of all
       mice tested. In a separate experiment, the level of spontaneous feline
       IgG production was quantified by ELISA 2 weeks after FIV inoculation
       with and without AZT treatment. Mean plasma feline IgG level of five
       SCID-fe mice inoculated with 10(3) TCID50 cell-free FIV was 2.23 mg
       ml-1. Mean feline IgG level of five mice inoculated with the same
       quantity of FIV and treated with AZT beginning 1 day prior to virus
       inoculation and continuing for 2 weeks thereafter was 14.98 mg ml-1. AZT
       significantly (P < 0.05) enhanced feline humoral immune function at a
       virus inoculum titer of 10(3) TCID50.(ABSTRACT TRUNCATED AT 400 WORDS)
 DE    Animal  Antibodies, Viral/BIOSYNTHESIS  Base Sequence  Cats  Chimera
       Disease Models, Animal  DNA Primers/CHEMISTRY  DNA, Viral/ANALYSIS
       Feline Acquired Immunodeficiency Syndrome/*DRUG THERAPY/
       IMMUNOLOGY/VIROLOGY  Female  IgG/BIOSYNTHESIS  Immunodeficiency Virus,
       Feline/DRUG EFFECTS/IMMUNOLOGY/  *PHYSIOLOGY  Lymphoid
       Tissue/TRANSPLANTATION/VIROLOGY  Mice  Mice, SCID  Molecular Sequence
       Data  Polymerase Chain Reaction/VETERINARY  Proto-Oncogene
       Proteins/ANALYSIS/GENETICS  Proto-Oncogenes  Proviruses/DRUG
       EFFECTS/IMMUNOLOGY/*PHYSIOLOGY  Severe Combined
       Immunodeficiency/COMPLICATIONS/IMMUNOLOGY/  *VETERINARY  Specific
       Pathogen-Free Organisms  Support, Non-U.S. Gov't  Support, U.S. Gov't,
       P.H.S.  Zidovudine/ADMINISTRATION & DOSAGE/PHARMACOLOGY/*THERAPEUTIC USE
       JOURNAL ARTICLE

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