Human immunodeficiency virus infection of human-PBL-SCID mice
Article Abstract:
Experiments were carried out to evaluate an animal model for use in AIDS research, the hu-PBL-SCID mouse. To develop the model, mice with the SCID (Severe Combined ImmunoDeficient) mutation, associated with a greatly reduced immune response, received transplanted human blood cells and were successfully infected with HIV-1 virus (human immunodeficiency virus, type 1), the virus associated with AIDS. Such a transfer of white blood cells (human peripheral blood leukocytes, or hu-PBLs) to SCID mice creates an animal called hu-PBL-SCID. These animals have a partially reconstituted immune system as a result of the cell transfer. The two main classes of immune system cells survive (T and B cells), human immunoglobulin (antibody protein) is produced, and secondary antibody responses can be elicited (those that occur after antigen and antibody bind). The hu-PBL-SCID mice were infected with HIV-1 virus, either as cell-free virus or as virus-infected immature T cells, and then evaluated to determine whether, in fact, infection occurred. Several experiments were performed to test this, including analyses of viral DNA from peritoneal (abdominal) fluid, and from spleen and lymph node cells. The virus appeared to replicate in the transplanted human cells. The minimal viral concentration necessary for infection was determined at different times after PBL reconstitution: this dose was greater eight weeks after reconstitution than two weeks afterwards. After infection, the reconstituted immune responses of the mice were impaired, as indicated by decreases in immunoglobulin levels and the number of CD4-positive T cells (a type of T cell which, if low levels are present, can indicate HIV infection in the human). This relatively simple animal model may be suitable for studying the effects of HIV-1 infection and for evaluating potential therapeutic approaches. (Consumer Summary produced by Reliance Medical Information, Inc.)
Publication Name: Science
Subject: Science and technology
ISSN: 0036-8075
Year: 1991
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Suppression of HIV infection in AZT-treated SCID-hu mice
Article Abstract:
The human immunodeficiency virus (HIV), which causes AIDS (acquired immunodeficiency syndrome), has been studied extensively and research is continuing. Although much has been learned about the virus itself, little is known about how the disease progresses within the body. At least part of this knowledge deficit follows from the lack of an animal model which can be conveniently studied in the laboratory. In order to provide such a model, genetically immunodeficient mice, designated scid/scid, were engrafted with human fetal organs. For example, in scid/scid mice engrafted with human fetal thymus, an organ necessary for the development of mature T-cells, human precursor cells can mature into functioning T-cells, despite their new location. The engrafted mice, called SCID-hu, can be infected with HIV and the progress of the infection experimentally monitored using the highly sensitive polymerase chain reaction or PCR. To determine whether the SCID-hu mice might serve as a useful tool for further research, AZT was injected into the mice 24 hours prior to HIV infection and treatment was continued for two weeks. At the end of this time PCR analysis of the mice indicated no HIV-specific reaction. All 40 untreated mice were positive for HIV products at this time. The SCID-hu mouse may provide a useful means for studying AIDS and its potential treatments; in addition, the same techniques may be applicable to the study of other viruses that show a preference for human immune-system tissues, such as cytomegalovirus, Epstein-Barr virus, and human T-cell leukemia virus. (Consumer Summary produced by Reliance Medical Information, Inc.)
Publication Name: Science
Subject: Science and technology
ISSN: 0036-8075
Year: 1990
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A model of human acute lymphoblastic leukemia in immune-deficient SCID mice
Article Abstract:
Acute lymphoblastic leukemia (ALL) of the non-T type is the most common leukemia in children. A living (in vivo) animal model for studying the growth and progression of ALL was devised using a special strain of mice. Immune-deficient SCID mice will assimilate healthy human cells and tumors that are grafted into their bodies. Cells taken from the blood of a patient in a terminal relapse of non-T ALL were transplanted into the mice. The human cells reproduced quickly in the hematopoietic tissues (tissues that generate blood cells). The cancer then entered different organs and killed the mice. Also, bone marrow from three human ALL patients caused leukemic cells to develop in the bone marrow and spleen of the mice. Distribution of leukemic cells within the mouse body mirrored the progression of ALL in children. In conclusion, the in vivo "laboratory" which was created in the SCID mouse should aid in the study of human leukemia and facilitate testing of experimental treatments. (Consumer Summary produced by Reliance Medical Information, Inc.)
Publication Name: Science
Subject: Science and technology
ISSN: 0036-8075
Year: 1989
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