Related Experiment Video
Updated: Aug 12, 2025
14:32
Deacetylation Assays to Unravel the Interplay between Sirtuins SIRT2 and Specific Protein-substrates
Published on: February 27, 2016
8.3K
Sirtuin-2, NAD-Dependent Deacetylase, Is a New Potential Therapeutic Target for HIV-1 Infection and HIV-Related
Clara Duran-Castells1,2, Anuska Llano1, Ai Kawana-Tachikawa3
1IrsiCaixa AIDS Research Institute, Hospital Germans Trias i Pujol, Badalona, Spain.
Journal of Virology
|January 31, 2023
Summary
Sirtuin-2 (SIRT2) is a novel biomarker for uncontrolled HIV infection, linked to neurological damage. Targeting SIRT2 with inhibitors reduced HIV replication and reactivation in vitro, offering a potential therapeutic strategy for HIV and associated neurocognitive disorders.
Area of Science:
- Virology
- Neuroscience
- Immunology
Background:
- Combined antiretroviral treatment (cART) has improved HIV management, but neurological comorbidities persist.
- Identifying plasma biomarkers for HIV-related neurological dysfunction is crucial for early detection and treatment.
- Sirtuin-2 (SIRT2), an NAD+-dependent deacetylase, is implicated in cellular processes relevant to HIV infection and neurological health.
Purpose of the Study:
- To identify plasma-based biomarkers associated with HIV replication and neurological damage in people living with HIV (PLWH).
- To investigate the role of sirtuin-2 (SIRT2) as a potential biomarker and therapeutic target in HIV infection.
- To evaluate the impact of cART initiation timing on SIRT2 levels and neurological health.
Main Methods:
- Customized antibody array used to analyze plasma factors in 40 untreated PLWH with varying viral loads.
- Longitudinal analysis of SIRT2 plasma levels in individuals with immediate versus delayed cART initiation.
- In vitro studies using small-molecule SIRT2 inhibitors on J-LAT A2 and primary glial cells to assess HIV replication and reactivation.
Main Results:
- Elevated plasma SIRT2 levels strongly correlated with higher viral loads, proviral DNA, and markers of neurological damage (SNCA, BDNF, MAPT, NFL).
- SIRT2 plasma levels differed between immediate and delayed cART initiation groups after one year and inversely correlated with brain orbitofrontal cortex involution.
- SIRT2 inhibition in vitro reduced HIV replication and virus reactivation from latency.
Conclusions:
- SIRT2 is identified as a novel biomarker for uncontrolled HIV infection and is associated with neurological dysfunction.
- Targeting SIRT2 presents a potential therapeutic strategy for managing HIV infection and its neurological complications.
- SIRT2 levels may serve as an indicator for the impact of cART timing on neurological health in PLWH.
Keywords:
HIV reservoirHIV-1HIV-associated neurocognitive disorders (HAND)neuroimagingneurological disorderplasma proteomicsvirus infection controlMore Related Videos
Related Concept Videos
02:30siRNA - Small Interfering RNAs
16.9K
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
16.9K
01:10Retrovirus Life Cycles
46.4K
Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the...
46.4K
01:20Antiepileptic Drugs: Modulators of Neurotransmitter Release Mediated by SV2A Protein
396
Antiepileptic drugs, such as levetiracetam (Keppra) and brivaracetam (Briviact), have emerged as crucial tools in managing epilepsy. These medications exert their therapeutic effects by targeting the synaptic vesicle protein SV2A, a transmembrane glycoprotein primarily found in the brain.
SV2A is a transmembrane glycoprotein located predominantly in the brain, modulating the release of neurotransmitters for neuronal communication. Both levetiracetam and brivaracetam exhibit a high affinity for...
SV2A is a transmembrane glycoprotein located predominantly in the brain, modulating the release of neurotransmitters for neuronal communication. Both levetiracetam and brivaracetam exhibit a high affinity for...
396