In vivo pathogenesis of a human immunodeficiency virus type 1 reporter virus.
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.
Jamieson
B D
BD
Division of Hematology-Oncology, Department of Medicine, UCLA School of Medicine and UCLA AIDS Institute, Los Angeles, California 90095-1678, USA.
Zack
J A
JA
D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics; D051927:CD24 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D015870:Gene Expression; D017930:Genes, Reporter; D005814:Genes, Viral; D005822:Genetic Vectors; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D008212:Lymphocyte Depletion; D008562:Membrane Glycoproteins; D051379:Mice; D016513:Mice, SCID; D011533:Proviruses / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000821:virology; D013950:Thymus Gland / Q000166:cytology; D014779:Virus Replication
D015703:Antigens, CD; D000943:Antigens, Differentiation; D051927:CD24 Antigen; C497889:CD24 protein, human; C497890:Cd24a protein, mouse; D008562:Membrane Glycoproteins