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Τρίτη 22 Μαΐου 2018

Anti-apoptotic Protein BIRC5 Maintains Survival of HIV-1-Infected CD4+ T Cells

Publication date: Available online 22 May 2018
Source:Immunity
Author(s): Hsiao-Hsuan Kuo, Rushdy Ahmad, Guinevere Q. Lee, Ce Gao, Hsiao-Rong Chen, Zhengyu Ouyang, Matthew J. Szucs, Dhohyung Kim, Athe Tsibris, Tae-Wook Chun, Emilie Battivelli, Eric Verdin, Eric S. Rosenberg, Steven A. Carr, Xu G. Yu, Mathias Lichterfeld
HIV-1 infection of CD4+ T cells leads to cytopathic effects and cell demise, which is counter to the observation that certain HIV-1-infected cells possess a remarkable long-term stability and can persist lifelong in infected individuals treated with suppressive antiretroviral therapy (ART). Using quantitative mass spectrometry-based proteomics, we showed that HIV-1 infection activated cellular survival programs that were governed by BIRC5, a molecular inhibitor of cell apoptosis that is frequently overexpressed in malignant cells. BIRC5 and its upstream regulator OX40 were upregulated in productively and latently infected CD4+ T cells and were functionally involved in maintaining their viability. Moreover, OX40-expressing CD4+ T cells from ART-treated patients were enriched for clonally expanded HIV-1 sequences, and pharmacological inhibition of BIRC5 resulted in a selective decrease of HIV-1-infected cells in vitro. Together, these findings suggest that BIRC5 supports long-term survival of HIV-1-infected cells and may lead to clinical strategies to reduce persisting viral reservoirs.

Graphical abstract

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Teaser

The host factors that promote the survival and persistence of HIV-infected CD4+ T cells are not clear. Kuo et al. demonstrate that the anti-apoptotic protein BIRC5 and its upstream regulator OX40 can promote survival of HIV-1-infected reservoir CD4+ T cells, specifically during clonal proliferation. These findings point to clinical strategies that may reduce persisting viral reservoirs.


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