Chemokine-receptor activation by env determines the mechanism of death in HIV-infected and uninfected T lymphocytes.
There is considerable confusion concerning the mechanism of lymphocyte death during HIV infection. During the course of HIV infection, M-tropic viruses (R5) that use CCR5 chemokine coreceptors frequently evolve to T-tropic viruses (X4) that use CXCR4 receptors. In this study we show that activation of the CD4 or CCR5 receptor by R5 HIVenv causes a caspase 8-dependent death of both uninfected and infected CD4 T cells. In contrast, CXCR4 activation by X4 HIVenv induces a caspase-independent death of both uninfected CD4 and CD8 T cells and infected CD4 cells. These results suggest that activation of the chemokine receptor by HIVenv determines the mechanism of death for both infected and uninfected T lymphocytes.
Vlahakis
S R
SR
Division of Infectious Diseases, Mayo Clinic, 200 First Street SW/GU-501, Rochester, Minnesota 55905, USA.
Algeciras-Schimnich
A
A
Bou
G
G
Heppelmann
C J
CJ
Villasis-Keever
A
A
Collman
R G
RG
Paya
C V
CV
D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology / Q000821:virology; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000502:physiology; D015752:Genes, env; D006678:HIV / Q000235:genetics*; D006801:Humans; D019713:Receptors, CCR5 / Q000502:physiology; D019718:Receptors, CXCR4 / Q000502:physiology; D019707:Receptors, Chemokine / Q000502:physiology*; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology*
D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases