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J Virol, August 1998, p. 6520-6526, Vol. 72, No. 8
Division of Hematology-Oncology,
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
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
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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