HIV-1-induced thymocyte depletion is associated with indirect cytopathogenicity and infection of progenitor cells in vivo.
Direct and indirect cytopathic mechanisms have been proposed to account for the loss of CD4+ T cells after infection with human immunodeficiency virus type 1 (HIV-1). We report here that HIV-1 infection of the human thymus in vivo results in thymocyte depletion by at least two different mechanisms. Thymocytes within multiple stages of differentiation are induced to die of apoptosis; most of these cells are uninfected. Additionally, thymopoiesis is interrupted by direct infection and destruction of intrathymic CD3-CD4+CD8- progenitor cells. These mechanisms are differentially induced by distinct isolates of HIV-1.
Su
L
L
HIV Group, Systemix, Incorporated, Palo Alto, California 94304, USA.
Kaneshima
H
H
Bonyhadi
M
M
Salimi
S
S
Kraft
D
D
Rabin
L
L
McCune
J M
JM
D000818:Animals; D017209:Apoptosis; D017252:CD3 Complex / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes; D016827:CD8 Antigens / Q000032:analysis; D002678:Chimera; D003588:Cytopathogenic Effect, Viral; D004253:DNA Nucleotidylexotransferase / Q000032:analysis; D015497:HIV-1 / Q000145:classification / Q000302:isolation & purification / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000473:pathology / Q000821:virology*; D006801:Humans; D018189:Immunomagnetic Separation; D016130:Immunophenotyping; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000302:isolation & purification; D016176:T-Lymphocyte Subsets / Q000473:pathology / Q000821:virology*; D013950:Thymus Gland / Q000473:pathology / Q000821:virology*
D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D004253:DNA Nucleotidylexotransferase