Skip to Main content Skip to Navigation
Journal articles

Anti-apoptotic clone 11 derived peptides induce in vitro death of CD4+ T cells susceptible to HIV-1 infection

Abstract : HIV-1 successfully establishes long-term infection in its target cells despite viral cytotoxic effects. We have recently shown that cell metabolism is an important factor driving CD4+ T-cell susceptibility to HIV-1 and the survival of infected cells. We show here that expression of anti-apoptotic clone 11 (AAC-11), an anti-apoptotic factor upregulated in many cancers, increased with progressive CD4+ T cell memory differentiation in association with the expression of cell cycle, activation and metabolism genes and correlated with susceptibility to HIV-1 infection. Synthetic peptides based on the LZ domain sequence of AAC-11, responsible for its interaction with molecular partners, were previously shown to be cytotoxic to cancer cells. Here we observed that these peptides also blocked HIV-1 infection by inducing cell death of HIV-1 susceptible primary CD4+ T-cells across all T-cell subsets. The peptides targeted metabolically active cells and had the greatest effect on effector and transitional CD4+ T cell memory subsets. Our results suggest that AAC-11 survival pathway is potentially involved in the survival of HIV-1 infectable cells and provide a proof of principle that some cellular characteristics can be targeted to eliminate the cells offering the best conditions to sustain HIV-1 replication.IMPORTANCE Although antiretroviral treatment efficiently blocks HIV multiplication, it cannot eliminate the cells already carrying integrated proviruses. In the search for a HIV cure the identification of new potential targets to selectively eliminate infected cells is of the outmost importance. We show here that peptides derived from the anti-apoptotic clone 11 (AAC-11), which expression levels correlated with susceptibility to HIV-1 infection of CD4+ T-cells, induced cytotoxicity in CD4+ T-cells showing the highest levels of activation and metabolic activity, conditions known to favor HIV-1 infection. Accordingly, CD4+ T-cells that survived the cytotoxic action of the AAC-11 peptides were resistant to HIV-1 replication. Our results identify a new potential molecular pathway to target HIV-1 infection.
Complete list of metadatas

https://hal-pasteur.archives-ouvertes.fr/pasteur-02612882
Contributor : Stevenn Volant <>
Submitted on : Tuesday, May 19, 2020 - 4:40:04 PM
Last modification on : Friday, June 26, 2020 - 4:14:05 PM

Links full text

Identifiers

Collections

Citation

Anastassia Mikhailova, Jose Carlos Valle-Casuso, Annie David, Valerie Monceaux, Stevenn Volant, et al.. Anti-apoptotic clone 11 derived peptides induce in vitro death of CD4+ T cells susceptible to HIV-1 infection. Journal of Virology, American Society for Microbiology, 2020, ⟨10.1128/JVI.00611-20⟩. ⟨pasteur-02612882⟩

Share

Metrics

Record views

42