Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
THE SCID-HU MOUSE AS A MODEL FOR HUMAN IMMUNODEFICIENCY VIRUS (HIV) INFECTION
The Human Retroviruses. Gallo RC and Jay G, eds. San Diego, Academic Press, p. 295-316, 1991.. Unique Identifier : AIDSLINE ICDB/92678732 Mc Cune JM; SyStemix, Inc., Palo Alto, CA 94303
Abstract:
A major obstacle to research on the role of HIV in AIDS has been the lack of an adequate model for HIV infection. An optimal model would be one in which HIV can be observed to infect human hematolymphoid organ systems within the confines of a mouse. Such a model has been developed in the form of the SCID-hu mouse. The rationale and process of development of the SCID-hu mouse are discussed under the following headings: the optimal model for HIV infection; construction of the SCID-hu mouse (animal husbandry, tissue collection, analysis, assay for function, and maintenance of human organ structures and hematopoiesis); infection of the SCID-hu mouse with HIV (general considerations, virus isolates, and systems for infection); current applications of the SCID-hu mouse to the analysis of HIV infection in humans (tropism, analysis of antiviral compounds, and analysis of vaccine candidates); and potential improvements of the SCID-hu mouse for the analysis of HIV infection in humans (demonstration of human immune function, analysis of multiple viral infections, immunologic standardization, and creation of safe systems for analysis). This animal model for the evaluation of human hematolymphoid differentiation was formed by the engraftment of human fetal liver, human fetal thymus, and human fetal lymph node into the C.B-17 scid/scid mouse, producing the hematochimeric SCID-hu mouse. The techniques used to create SCID-hu individuals do not yield 100% success rates. Sufficiently large numbers of animals must be analyzed in any experiment to ensure that statistically meaningful statements can be made. Some observations concerning immune function that have been made so far in this system include (1) an absence of graft-vs-host disease, with normal CD4/CD8 ratio in the peripheral blood and an absence of activation antigens on human T cells; (2) a phenotypic and functional similarity between the T cells in SCID-hu mice and normal human T cells; and (3) eliciting of human antibody responses by antigens intentionally introduced into the SCID-hu mouse. In much the same way that empirical experimentation led to established protocols for immunization of rabbits, numerous variables are now being approached in the SCID-hu. If human immune functions can be elicited in a practical manner, many questions can be asked concerning T-cell and B-cell functions and active immunization against HIV. (63 Refs)
Keywords: Animal Antiviral Agents/ADMINISTRATION & DOSAGE AIDS Vaccines/IMMUNOLOGY Gene Expression Regulation, Viral/*PHYSIOLOGY Human HIV/*GENETICS/IMMUNOLOGY/PATHOGENICITY HIV Infections/*GENETICS/IMMUNOLOGY/MICROBIOLOGY Mice Mice, SCID/*GENETICS Murine Acquired Immunodeficiency Syndrome/*GENETICS/IMMUNOLOGY/ MICROBIOLOGY Opportunistic Infections/GENETICS/IMMUNOLOGY/MICROBIOLOGY Phenotype T-Lymphocytes/IMMUNOLOGY Virus Replication/DRUG EFFECTS/GENETICS/IMMUNOLOGY MONOGRAPH REVIEW
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Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
