Hiv-1 tat activates akt/mtorc1 pathway and aicda expression by downregulating its transcriptional inhibitors in b cells

Akbay B. Germini D. Bissenbaev A.K. Musinova Y.R. Sheval E.V. Vassetzky Y. Dokudovskaya S.
February 2021 MDPI AG

International Journal of Molecular Sciences
2021 #22 Issue 4 1 - 12 pp.

HIV-1 infects T cells, but the most frequent AIDS-related lymphomas are of B-cell origin. Molecular mechanisms of HIV-1-induced oncogenic transformation of B cells remain largely unknown. HIV-1 Tat protein may participate in this process by penetrating and regulating gene expression in B cells. Both immune and cancer cells can reprogram communications between extracellular signals and intracellular signaling pathways via the Akt/mTORC1 pathway, which plays a key role in the cellular response to various stimuli including viral infection. Here, we investigated the role of HIV-1 Tat on the modulation of the Akt/mTORC1 pathway in B cells. We found that HIV-1 Tat activated the Akt/mTORC1 signaling pathway; this leads to aberrant activation of activation-induced cytidine deaminase (AICDA) due to inhibition of the 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.

AICDA , Akt/mTORC1 pathway , B cells , HIV-1 , Tat

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CNRS UMR9018, Institut Gustave Roussy, Université Paris-Saclay, Villejuif, 94805, France
Department of Molecular Biology and Genetics, Faculty of Biology and Biotechnology, al-Farabi Kazakh National University, Almaty, 050040, Kazakhstan
Scientific Research Institute of Biology and Biotechnology Problems, al-Farabi Kazakh National University, Almaty, 050040, Kazakhstan
Koltzov Institute of Developmental Biology of Russian Academy of Sciences, Moscow, 119991, Russian Federation
Belozersky Institute of Physicochemical Biology, Moscow State University, Moscow, 119899, Russian Federation

CNRS UMR9018
Department of Molecular Biology and Genetics
Scientific Research Institute of Biology and Biotechnology Problems
Koltzov Institute of Developmental Biology of Russian Academy of Sciences
Belozersky Institute of Physicochemical Biology

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