HIV-1 Tat Activates Akt/mTORC1 Pathway and AICDA Expression by Downregulating Its Transcriptional Inhibitors in B Cells

Burkitkan Akbay (1, 2) , Diego Germini (1) , Amangeldy K Bissenbaev (2) , Yana R Musinova (3, 4) , Evgeny V Sheval (4) , Yegor Vassetzky (1, 5) , Svetlana Dokudovskaya (1, 5)

1 METSY - Aspects métaboliques et systémiques de l'oncogénèse pour de nouvelles approches thérapeutiques
2 KazNU - Al-Farabi Kazakh National University [Almaty]
3 Koltzov Institute of Developmental Biology
4 Belozersky Institute of Physico-Chemical Biology
5 UMR8126 - Signalisation, noyaux et innovations en cancérologie

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 activationinduced 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.

Mots clés: HIV-1; Tat; Akt/mTORC1 pathway; AICDA; B cells; HIV-1

Domaines: Maladies infectieuses; Cancer; Génomique, Transcriptomique et Protéomique [q-bio.GN]; Virologie

Burkitkan Akbay, Diego Germini, Amangeldy K Bissenbaev, Yana R Musinova, Evgeny V Sheval, et al.. HIV-1 Tat Activates Akt/mTORC1 Pathway and AICDA Expression by Downregulating Its Transcriptional Inhibitors in B Cells. International Journal of Molecular Sciences, 2021, 22 (4), pp.1588. ⟨10.3390/ijms22041588⟩. ⟨hal-03375919⟩