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Updated: May 9, 2025
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High Throughput In Vitro Assessment of Latency Reversing Agents on HIV Transcription and Splicing
Published on: January 22, 2019
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Backsplicing of the HIV-1 transcript generates multiple circRNAs to promote viral replication
Christopher Mauer1, Sean Paz1, Massimo Caputi2
1Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, USA.
Npj Viruses
|April 28, 2025
Summary
Human immunodeficiency virus type 1 (HIV-1) generates circular RNAs (circRNAs) that enhance viral replication. These HIV circRNAs sequester cellular microRNAs (miRNAs), hindering their antiviral functions and promoting infection.
Area of Science:
- Virology
- Molecular Biology
- RNA Biology
Background:
- Circular RNAs (circRNAs) are non-coding RNAs formed by backsplicing.
- Human immunodeficiency virus type 1 (HIV-1) exhibits complex splicing patterns.
- The role of circRNAs in viral replication is an emerging area of research.
Purpose of the Study:
- To investigate the potential generation and function of circRNAs in HIV-1 infection.
- To identify specific circRNAs produced by HIV-1 and their interactions with cellular microRNAs (miRNAs).
- To elucidate the impact of these circRNA-miRNA interactions on HIV-1 replication.
Main Methods:
- Analysis of HIV-1 splicing patterns to predict circRNA formation.
- Amplification and confirmation of predicted HIV circRNAs using PCR, RNase R digestion, and sequencing.
- Computational modeling and experimental validation of circRNA-miRNA interactions.
- Assessment of viral replication in response to altered circRNA and miRNA expression.
Main Results:
- HIV-1 can generate at least 15 distinct circRNAs.
- Two cellular miRNAs, miR-6727-3p and miR-4722-3p, interact with sequences in 8 HIV circRNAs.
- Expression of these miRNAs restricts HIV-1 replication.
- HIV circRNAs containing the miRNA-binding sequence enhance infectious virion production.
- miR-6727-3p and miR-4722-3p expression increases upon HIV-1 infection of CD4+ T cells.
Conclusions:
- HIV-1 produces circRNAs that promote viral replication.
- These HIV circRNAs function by sequestering and inhibiting antiviral cellular miRNAs (miR-6727-3p and miR-4722-3p).
- This mechanism represents a novel strategy employed by HIV-1 to enhance its replication cycle.
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