Document 0898
 DOCN  M9440898
 TI    Disseminated human immunodeficiency virus 1 (HIV-1) infection in SCID-hu
       mice after peripheral inoculation with HIV-1.
 DT    9404
 AU    Kollmann TR; Pettoello-Mantovani M; Zhuang X; Kim A; Hachamovitch M;
       Smarnworawong P; Rubinstein A; Goldstein H; Department of Microbiology
       and Immunology, Albert Einstein; College of Medicine, Bronx, New York
       10461.
 SO    J Exp Med. 1994 Feb 1;179(2):513-22. Unique Identifier : AIDSLINE
       MED/94125032
 AB    A small animal model that could be infected with human immunodeficiency
       virus 1 (HIV-1) after peripheral inoculation would greatly facilitate
       the study of the pathophysiology of acute HIV-1 infection. The utility
       of SCID mice implanted with human fetal thymus and liver (SCID-hu mice)
       for studying peripheral HIV-1 infection in vivo has been hampered by the
       requirement for direct intraimplant injection of HIV-1 and the continued
       restriction of the resultant HIV-1 infection to the human thymus and
       liver (hu-thy/liv) implant. This may have been due to the very low
       numbers of human T cells present in the SCID-hu mouse peripheral
       lymphoid compartment. Since the degree of the peripheral reconstitution
       of SCID-hu mice with human T cells may be a function of the hu-thy/liv
       implant size, we increased the quantity of hu-thy/liv tissue implanted
       under the renal capsule and implanted hu-thy/liv tissue under the
       capsules of both kidneys. This resulted in SCID-hu mice in which
       significant numbers of human T cells were detected in the peripheral
       blood, spleens, and lymph nodes. After intraimplant injection of HIV-1
       into these modified SCID-hu mice, significant HIV-1 infection was
       detected by quantitative coculture not only in the hu-thy/liv implant,
       but also in the spleen and peripheral blood. This indicated that HIV-1
       infection can spread from the thymus to the peripheral lymphoid
       compartment. More importantly, a similar degree of infection of the
       hu-thy/liv implant and peripheral lymphoid compartment occurred after
       peripheral intraperitoneal inoculation with HIV-1. Active viral
       replication was indicated by the detection of HIV-1 gag DNA, HIV-1 gag
       RNA, and spliced tat/rev RNA in the hu-thy/liv implants, peripheral
       blood mononuclear cells (PBMC), spleens, and lymph nodes of these
       HIV-1-infected SCID-hu mice. As a first step in using our modified
       SCID-hu mouse model to investigate the pathophysiological consequences
       of HIV-1 infection, the effect of HIV-1 infection on the expression of
       human cytokines shown to enhance HIV-1 replication was examined.
       Significantly more of the HIV-1-infected SCID-hu mice expressed mRNA for
       human tumor necrosis factors alpha and beta, and interleukin 2 in their
       spleens, lymph nodes, and PBMC than did uninfected SCID-hu mice. This
       suggested that HIV-1 infection in vivo can stimulate the expression of
       cytokine mRNA by human T cells.(ABSTRACT TRUNCATED AT 400 WORDS)
 DE    Animal  Base Sequence  Cell Transplantation  Chimera
       Cytokines/BIOSYNTHESIS/GENETICS  *Disease Models, Animal  DNA  Gene
       Expression  Human  HIV Infections/IMMUNOLOGY/*PHYSIOPATHOLOGY
       *HIV-1/GENETICS/ISOLATION & PURIF  Liver/CYTOLOGY  Mice  Mice, SCID
       Molecular Sequence Data  Support, Non-U.S. Gov't  Support, U.S. Gov't,
       P.H.S.  T-Lymphocytes/TRANSPLANTATION  Thymus Gland/CYTOLOGY  JOURNAL
       ARTICLE

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