HIV-1 Tat Activates Akt/mTORC1 Pathway and AICDA Expression by Downregulating Its Transcriptional Inhibitors in B Cells.
Burkitkan AkbayDiego GerminiAmangeldy K BissenbaevYana R MusinovaEvgeny V ShevalYegor S VassetzkySvetlana DokudovskayaPublished in: International journal of molecular sciences (2021)
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.
Keyphrases
- signaling pathway
- antiretroviral therapy
- hiv positive
- hiv infected
- hiv testing
- human immunodeficiency virus
- gene expression
- hepatitis c virus
- hiv aids
- men who have sex with men
- cell proliferation
- transcription factor
- pi k akt
- epithelial mesenchymal transition
- induced apoptosis
- south africa
- mass spectrometry
- drug induced
- small molecule
- dna methylation
- copy number
- binding protein