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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...
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Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
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Updated: Jan 11, 2026

Evaluation of the Efficacy And Toxicity of RNAs Targeting HIV-1 Production for Use in Gene or Drug Therapy
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Targeting HIV-1 transcription: road to a cure?

Liset de Vries1, Robert-Jan Palstra1, Tokameh Mahmoudi1,2

  • 1Department of Pathology, Erasmus University Medical Center, Rotterdam, The Netherlands.

Transcription
|November 14, 2025
PubMed
Summary

Understanding Human Immunodeficiency Virus 1 (HIV-1) latency is key to an HIV cure. New research reveals co- and post-transcriptional blocks, alongside transcriptional ones, are crucial for HIV-1 gene regulation and reservoir persistence.

Keywords:
HIV-1LRAblock and locklatencytranscription

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Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • Human Immunodeficiency Virus 1 (HIV-1) causes AIDS, but antiretroviral therapy (ART) manages it as a chronic condition.
  • HIV-1 cure remains elusive due to latent reservoirs of infected cells, with latency mechanisms primarily studied at the transcriptional level.

Purpose of the Study:

  • To summarize established and novel mechanisms of HIV-1 latency, focusing on transcriptional, co-transcriptional, and post-transcriptional regulation.
  • To discuss the implications of these mechanisms for developing latency reversal agents (LRAs) and HIV-1 cure strategies.
  • To highlight advancements in technologies for ex vivo characterization of the HIV-1 reservoir.

Main Methods:

  • Review of existing literature on HIV-1 latency mechanisms.
  • Analysis of clinical study outcomes for LRAs.
  • Description of novel ex vivo technologies for reservoir characterization (e.g., analyzing proviral DNA, RNA splicing, and protein levels).

Main Results:

  • Latency reversal agents (LRAs) have shown limited success in reactivating the viral reservoir sufficiently for protein production or reducing reservoir size.
  • Co- and post-transcriptional mechanisms play significant roles in regulating HIV-1 gene expression and may represent alternative therapeutic targets.
  • New technologies provide deeper insights into the molecular compartments of the HIV-1 reservoir.

Conclusions:

  • A comprehensive understanding of HIV-1 latency requires considering transcriptional, co-transcriptional, and post-transcriptional regulatory layers.
  • Targeting these multiple regulatory blocks is essential for effective HIV-1 cure strategies.
  • Advancements in reservoir characterization technologies are crucial for evaluating the efficacy of novel cure interventions, including those combined with Long Acting (LA)-ART.