Modulation of mTORC1 Signaling Pathway by HIV-1

Akbay, Burkitkan; Шмакова, А. А.; Vassetzky, Yegor S.; Dokudovskaya, Svetlana

doi:10.3390/cells9051090

Cited by 28 publications

(29 citation statements)

References 136 publications

(179 reference statements)

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“…HIV-1 Env can activate the MTORC1 complex resulting in efficient viral replication and viral production. In fact, HIV-1 infection increases MTORC1 activity in both productively infected and bystander cells (Akbay et al, 2020).…”

Section: Autophagy and Early Hiv-1 Infection In Macrophages And Dendritic Cellsmentioning

confidence: 99%

“…Another drug, LY 294002 that inhibits PIK3 class I as well as MTORC1, suppresses viral infection of macrophages in post-entry and post-reverse transcription steps prior to HIV-1 gene expression (François and Klotman, 2003). Pan-inhibitors of MTORC1 neutralize HIV-1 infection by interfering with viral entry in humanized mouse in vivo models, since these inhibitors decrease CCR5 levels at the cell-surface of target cells, and also act during viral transcription (Heredia et al, 2015;Akbay et al, 2020). Likewise, other research showed that HIV-1 gp41-induced apoptosis is mediated by caspase-3-dependent mitochondrial production of ROS (Garg and Blumenthal, 2006), which acts as a stimulus to sustain the autophagy process (Levonen et al, 2014;Filomeni et al, 2015).…”

Section: The Effect Of Autophagy Modulation In the Early Steps Of Hiv-1 Infectionmentioning

confidence: 99%

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The Interplay of HIV and Autophagy in Early Infection

et al. 2021

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HIV/AIDS is still a global threat despite the notable efforts made by the scientific and health communities to understand viral infection, to design new drugs or to improve existing ones, as well as to develop advanced therapies and vaccine designs for functional cure and viral eradication. The identification and analysis of HIV-1 positive individuals that naturally control viral replication in the absence of antiretroviral treatment has provided clues about cellular processes that could interact with viral proteins and RNA and define subsequent viral replication and clinical progression. This is the case of autophagy, a degradative process that not only maintains cell homeostasis by recycling misfolded/old cellular elements to obtain nutrients, but is also relevant in the innate and adaptive immunity against viruses, such as HIV-1. Several studies suggest that early steps of HIV-1 infection, such as virus binding to CD4 or membrane fusion, allow the virus to modulate autophagy pathways preparing cells to be permissive for viral infection. Confirming this interplay, strategies based on autophagy modulation are able to inhibit early steps of HIV-1 infection. Moreover, autophagy dysregulation in late steps of the HIV-1 replication cycle may promote autophagic cell-death of CD4+ T cells or control of HIV-1 latency, likely contributing to disease progression and HIV persistence in infected individuals. In this scenario, understanding the molecular mechanisms underlying HIV/autophagy interplay may contribute to the development of new strategies to control HIV-1 replication. Therefore, the aim of this review is to summarize the knowledge of the interplay between autophagy and the early events of HIV-1 infection, and how autophagy modulation could impair or benefit HIV-1 infection and persistence, impacting viral pathogenesis, immune control of viral replication, and clinical progression of HIV-1 infected patients.

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Section: Autophagy and Early Hiv-1 Infection In Macrophages And Dendritic Cellsmentioning

confidence: 99%

Section: The Effect Of Autophagy Modulation In the Early Steps Of Hiv-1 Infectionmentioning

confidence: 99%

The Interplay of HIV and Autophagy in Early Infection

et al. 2021

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“…HIV infection is associated with an elevated risk of developing AIDS-defining cancers, including a number of B-cell lymphomas [ 9 , 10 ]. Even though a current antiretroviral therapy is quite efficient, a high incidence of HIV-1-associated malignancies persists and the mechanism of development of these diseases is largely unclear [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

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

Akbay

Germini

Bissenbaev

et al. 2021

IJMS

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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.

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“…This miRNA targets AKT and mTOR, central components of the mTORC1 complex [76]. A double suppression of the mTOR pathway helps in the early stage of HIV infection, blocking the entry to the cell through CCR5 recycling and interfering with induced and basal transcription [77]. Although only one DE miRNA is regulated similarly in HESN compared to our LTNP patients, it should be noticed that resistance mechanisms in HESN may differ from those of LTNPs since the latter regulates disease progression and HESN is probably involved in HIV-1 acquisition.…”

Section: Discussionmentioning

confidence: 99%

Insight in miRNome of Long-Term Non-Progressors and Elite Controllers Exposes Potential RNAi Role in Restraining HIV-1 Infection

Ayala-Suárez

Díez-Fuertes

Calonge

et al. 2020

JCM

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Long-term non-progressors (LTNP) and elite controllers (EC) represent spontaneous natural models of efficient HIV-1 response in the absence of treatment. The main purposes of this work are to describe the miRNome of HIV-1 infected patients with different extreme phenotypes and identify potentially altered pathways regulated by differentially expressed (DE) miRNAs. The miRNomes from peripheral blood mononuclear cells (PBMCs) of dual phenotype EC-LTNP or LTNP with detectable viremia and HIV-infected patients with typical progression before and after treatment, were obtained through miRNA-Seq and compared among them. The administration of treatment produces 18 DE miRNAs in typical progressors. LTNP condition shows 14 DE miRNA when compared to typical progressors, allowing LTNP phenotype differentiation. A set of four miRNAs: miR-144-3p, miR-18a-5p, miR-451a, and miR-324 is strongly downregulated in LTNP and related to protein regulation as AKT, mTOR, ERK or IKK, involved in immune response pathways. Deregulation of 28 miRNA is observed between EC-LTNP and viremic-LTNP, including previously described anti-HIV miRNAs: miR-29a, associated with LTNP phenotype, and miR-155, targeting different pre-integration complexes such as ADAM10 and TNPO3. A holistic perspective of the changes observed in the miRNome of patients with different phenotypes of HIV-control and non-progression is provided.

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Modulation of mTORC1 Signaling Pathway by HIV-1

Cited by 28 publications

References 136 publications

The Interplay of HIV and Autophagy in Early Infection

The Interplay of HIV and Autophagy in Early Infection

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

Insight in miRNome of Long-Term Non-Progressors and Elite Controllers Exposes Potential RNAi Role in Restraining HIV-1 Infection

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