In Vivo Pathogenesis of a Human Immunodeficiency Virus Type 1 Reporter Virus |
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Authors: | Beth D Jamieson and Jerome A Zack |
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Institution: | Division of Hematology-Oncology, Department of Medicine,1. and Department of Microbiology and Molecular Genetics,2. UCLA School of Medicine and UCLA AIDS Institute, Los Angeles, California 90095-1678 |
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Abstract: | Our understanding of human immunodeficiency virus type 1 (HIV-1)-induced pathogenesis is hampered by the inability to detect HIV-1 gene expression in infected viable cells. In this report, we describe two HIV-1 reporter constructs that are replication competent and cytopathic in vivo. These constructs contain DNA regions of two different lengths that bear the cDNA for the murine heat-stable antigen in the vpr region of a CXCR4-tropic virus. We used the SCID-hu mouse model and these reporter viruses to perform detailed kinetic studies of HIV-1 infection of human thymocytes in vivo. We document that the CD4+/CD8+ thymocytes are the first to express virus and that this subset demonstrates the most rapid and extensive HIV-1-induced cell depletion. Following depletion of this subset, subsequent virus expression occurs predominantly in phenotypically CD4− cells, suggesting that CD4 down-regulation occurs in HIV-1-infected thymocytes in vivo. These results demonstrate the utility of these HIV-1 reporter constructs to monitor HIV pathogenesis in vitro and in vivo. |
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