Apoptosis induced in synchronized human immunodeficiency virus type 1-infected primary peripheral blood mononuclear cells is detected after the peak of CD4+ T-lymphocyte loss and is dependent on the tropism of the gp120 envelope glycoprotein.
Disease progression in human immunodeficiency virus type-1 (HIV-1)-infected individuals is frequently accompanied by declining CD4 cell numbers and the acquisition of a T-tropic (X4) or dual tropic (R5X4) phenotype. Understanding the mechanism of CD4 cell loss in HIV-1 infection is essential for the development of effective therapeutic strategies. In this study, donor populations of peripheral blood mononuclear cells (PBMCs) were selected for their ability to support an equivalent acute infection by both R5 and X4 virus phenotypes. This demonstrated that CD4+ T-lymphocyte loss was due to the gp120 region of Env and was replication independent. Furthermore, apoptosis was only detected in cells infected with an X4 virus after the majority of CD4+ T-lymphocyte loss had occurred. These observations indicate that the CD4+ T-lymphocyte loss in an X4 HIV-1 infection is not directly mediated by apoptosis, although apoptosis may be induced in the remaining cell population as a consequence of this CD4+ T-lymphocyte loss.
Lawson
Victoria A
VA
AIDS Cellular Biology Laboratory, Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, Australia.
Silburn
Katherine A
KA
Gorry
Paul R
PR
Paukovic
Geza
G
Purcell
Damian F J
DF
Greenway
Alison L
AL
McPhee
Dale A
DA
D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology* / Q000821:virology; D002478:Cells, Cultured; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015497:HIV-1 / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000502:physiology* / Q000821:virology; D008213:Lymphocyte Activation; D019718:Receptors, CXCR4 / Q000378:metabolism*; D014779:Virus Replication
D015699:HIV Envelope Protein gp120; D019718:Receptors, CXCR4