Increased rate of HIV-1 entry and its cytopathic effect in CD4+/CXCR4+ T cells expressing relatively high levels of CD26.
The role of the T-cell activation antigen CD26 was evaluated in viral entry and infection of CD4(+)/CXCR4(+) cells by the lymphotropic HIV-1 Lai isolate. For this purpose, CEM T cells, which are permissive to HIV infection and express low levels of CD26, were used to establish by transfection four groups of cell clones expressing either low, high, and very high levels of CD26, or expressing the anti-sense RNA of CD26. Entry was monitored by the detection of proviral DNA synthesis and the kinetics of virus production, whereas the cytopathic effect was demonstrated by the occurrence of apoptosis. HIV entry and infection were consistently accelerated by at least 24 to 48 h in clones expressing high levels of CD26 compared to the parental cells or to the clones expressing low levels of CD26. Interestingly, infection of clones expressing very high levels of CD26 was not accelerated and showed a kinetics of infection similar to that of low CD26 expressing clones. Moreover, HIV infection was significantly reduced in the clones expressing CD26 anti-sense RNA. In the different clones, apoptosis was dependent on the severity of virus infection and occurred after the accumulation of HIV envelope glycoproteins. Our results demonstrate that with equivalently expressed levels of CD4 and CXCR4 in cell lines established from CEM cells, relatively high levels of CD26 contribute to an increased rate of HIV entry, infection, and apoptosis. Furthermore, they point out that overexpression of CD26 in a given cell line may lead to a negative effect on HIV infection. Consequently, CD26 appears to regulate HIV entry and apoptosis, processes which are critical for viral pathogenesis.
Callebaut
C
C
ERS 572 CNRS, Institut Pasteur, 28, rue du Dr. Roux, Paris cedex 15, 75724, France.
Jacotot
E
E
Blanco
J
J
Krust
B
B
Hovanessian
A G
AG
D015704:CD4 Antigens / Q000096:biosynthesis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D016923:Cell Death / Q000276:immunology; D002460:Cell Line; D018819:Dipeptidyl Peptidase 4 / Q000096:biosynthesis / Q000276:immunology*; D005434:Flow Cytometry; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D016130:Immunophenotyping; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000821:virology; D014779:Virus Replication / Q000276:immunology*
D015704:CD4 Antigens; D019718:Receptors, CXCR4; D018819:Dipeptidyl Peptidase 4