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Regulation of the Akt/mTORC1 Pathway by HIV Transcriptional Activator Tat in B Cells

Abstract : Aggressive B cell lymphomas are the main cause of death in HIV-1 infected individuals, although B cells are not targeted by the virus. The exact mechanisms of the development of these lymphomas are not known. Previous studies of our team revealed that HIV-1 Tat can penetrate B cells, where it can induce ROS production, DNA damage and increase the chances of the oncogenic translocations specific for Burkitt lymphoma. In addition in many immune cells HIV-1 and its proteins (e.g. Tat) can regulate Akt/mTORC1 pathway, a central integrator of many intra and extracellular signals including viral infection and DNA damage. However, no studies have examined the regulation of Akt/mTORC1 pathway by Tat in B cells. In this thesis I have tested the hypothesis that HIV-1 Tat might produce oncogenic effects in B cells by modulating Akt/mTORC1 signaling pathway and regulating expression of genes involved in lymphomagenesis. I found that HIV-1 Tat activated Akt/mTORC1 signaling pathway, which leads to aberrant activation of AICDA (activation induced cytidine deaminase) due to inhibition of AICDA transcriptional repressors c-Myb and E2F8. These perturbations may ultimately lead to an increased genomic instability and proliferation that might cause B cell malignancies.
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Submitted on : Tuesday, May 4, 2021 - 12:21:17 PM
Last modification on : Thursday, May 6, 2021 - 10:54:13 AM

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  • HAL Id : tel-03216741, version 1

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Burkitkan Akbay. Regulation of the Akt/mTORC1 Pathway by HIV Transcriptional Activator Tat in B Cells. Cancer. Université Paris-Saclay; Al-Farabi Kazakh National University (Almaty, Kazakhstan), 2021. English. ⟨NNT : 2021UPASL026⟩. ⟨tel-03216741⟩

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