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J Virol, August 1998, p. 6520-6526, Vol. 72, No. 8
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

In Vivo Pathogenesis of a Human Immunodeficiency Virus Type 1 Reporter Virus

Beth D. Jamieson1 and Jerome A. Zack1,2,*

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

Received 5 March 1998/Accepted 12 May 1998

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.


* Corresponding author. Mailing address: Departments of Medicine and Microbiology and Molecular Genetics, UCLA School of Medicine and UCLA AIDS Institute, 11-934 Factor Bldg., Box 951678, Los Angeles, CA 90095-1678. Phone: (310) 794-7765. Fax: (310) 825-6192. E-mail: jzack{at}ucla.edu.


J Virol, August 1998, p. 6520-6526, Vol. 72, No. 8
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.



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