HIV-1 Pathogenesis and Therapeutic Intervention in the SCID-hu Thy/Liv Mouse: a Model for Primary HIV-1 Infection in the Human Thymus

Overview

Journal Rev Med Virol

Publisher Wiley

Specialty Microbiology

Date 1999 Jul 9

PMID 10398480

Citations 5

Authors

Affiliations

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Abstract

The SCID-hu Thy/Liv mouse is a model for the analysis of human thymopoiesis. It has been constructed by engrafting fragments of human fetal liver and thymus into the immunodeficient C.B-17 scid/scid (SCID) mouse. The resulting 'Thy/Liv' organ promotes long-term differentiation of human T cells. Given the apparently normal physiology of the SCID-hu Thy/Liv organ, it has been used to explore the pathophysiologic mechanisms of HIV-1 infection in vivo, and to test therapeutic modalities such as anti-HIV-1 drugs and haematopoietic stem cell (HSC)-based gene therapy. In this review, I will summarise what we have learned from the SCID-hu Thy/Liv model, with a focus on recent findings in HIV-1 replication and therapy. Unique HIV-1 determinants have been identified which are required for replication in the Thy/Liv organ but not for replication in PBMC or in T cell lines in vitro. The mechanism of HIV-1 induced thymus depletion is not clear. It is correlated with high levels of HIV-1 replication. Both direct and indirect mechanisms may be involved. In addition to preclinical evaluation of anti- HIV-1 drugs, the SCID-hu Thy/Liv mouse has also been successfully used to test the feasibility of HSC-based gene therapy. A number of improved SCID-hu models have been constructed to meet different requirements. Using these SCID-hu Thy/Liv models, current/future efforts will provide insightful information for understanding pathogenesis and designing therapeutic interventions against HIV-1 infection in humans, especially in paediatric patients. Copyright 1997 John Wiley & Sons, Ltd.

Citing Articles

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Fusion-induced apoptosis contributes to thymocyte depletion by a pathogenic human immunodeficiency virus type 1 envelope in the human thymus.

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HIV-1 replication and pathogenesis in the human thymus.

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Induction of MHC class I expression on immature thymocytes in HIV-1-infected SCID-hu Thy/Liv mice: evidence of indirect mechanisms.

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