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The level of CD26 determines the rate of HIV entry in a CD4+ T-cell line
C Callebaut1, E Jacotot, J Blanco
1Unité de Virologie et Immunologie Cellulaire, Institut Pasteur, Paris, France. chrcall@pasteur.fr
Insights
CD26 acts as a cofactor in HIV entry. Its levels influence HIV infection rates and cell damage, with specific expression levels impacting viral replication and apoptosis.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- CD26 (dipeptidyl peptidase 4) has emerged as a significant factor in HIV pathogenesis.
- Previous research indicated CD26's role as a cofactor for CD4 in HIV entry.
- Evidence links CD26 to HIV replication, cytopathic effects, and HIV-envelope-induced apoptosis.
Purpose of the Study:
- To investigate the precise role of CD26 levels in HIV entry and replication.
- To determine how varying CD26 expression affects HIV-induced cytopathic effects and apoptosis.
Main Methods:
- Utilized CEM T-cell lines transfected to express differential levels of CD26.
- Established clones with varying CD26 expression: CD26-High, CD26-Low, CD26-SuperHigh, and CD26-AntiSense.
- Monitored HIV entry, infection rates, and cytopathic effects in these engineered cell lines.
Main Results:
- HIV entry, infection, and cytopathic effects were delayed in CD26-Low and CD26-SuperHigh clones compared to CD26-High clones.
- The most significant delay in viral progression and absence of cytopathic effect was observed in CD26-AntiSense clones.
- CD26-SuperHigh clones exhibited a phenotype similar to CD26-Low clones, suggesting a complex regulatory role.
Conclusions:
- Enhanced CD26 levels correlate with increased HIV infection rates.
- CD26 plays a critical role in modulating the kinetics of HIV entry and subsequent cytopathic effects.
- The interaction between HIV envelope glycoproteins, CD4, and CD26 is crucial for initiating viral entry and pathogenesis.
Abstract:
We have reported that CD26 could serve as a cofactor of CD4 in HIV entry. Recently, more evidence has been provided for the implication of CD26 in HIV entry, replication and cytopathic effect. Along with, we have demonstrated that the level of CD26 may determine the rate of HIV-envelope induced-apoptosis. The role of CD26 in HIV entry was further investigated using CEM T-cell line. Clones were established by transfection, expressing different levels of CD26. Entry, infection and cytopathic effect were monitored in several independent clones, and were found to be delayed in clones CD26-Low and CD26-SuperHigh compared to clones CD26-High. The delay was most significant in clones CD26-AntiSense, without any apparent cytopathic effect. These results demonstrate that relatively enhanced levels of CD26 contribute to an increased virus infection. Furthermore, they illustrate that CD26-SuperHigh clones manifest a phenotype similar to CD26-Low clones. This point out the critical role of CD26 in the rate of HIV entry and its cytopathic effect, two events which are initiated by the interaction of HIV envelope glycoproteins with cell-surface CD4.