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Updated: May 3, 2026

Identification of Nucleolar Factors During HIV-1 Replication Through Rev Immunoprecipitation and Mass Spectrometry
Published on: June 26, 2019
A role for H/ACA and C/D small nucleolar RNAs in viral replication
James L Murray1, Jinsong Sheng, Donald H Rubin
1Zirus, Inc., 1384 Buford Business Boulevard, Suite 700, Buford, GA, 30518, USA, jmurray100@yahoo.com.
Gene-trap mutagenesis identified over 1,000 host genes conferring virus resistance. Small nucleolar RNAs (SNORAs and SNORDs) were found to play a significant role in cellular defense against multiple viral infections.
Area of Science:
- Virology
- Genetics
- Molecular Biology
Background:
- Identifying host factors that restrict viral infections is crucial for understanding virus-host interactions.
- Gene-trap insertional mutagenesis is a powerful tool for discovering novel genes involved in cellular processes.
Purpose of the Study:
- To identify host genes conferring resistance to lytic viral infection using a large-scale mutagenesis screen.
- To investigate the role of small nucleolar RNAs (SNORAs and SNORDs) in antiviral defense.
Main Methods:
- Employed gene-trap insertional mutagenesis across 12 viruses and multiple cell lines to generate virus-resistant clones.
- Analyzed over 2,000 resistant clones to identify disrupted candidate host genes.
- Utilized small interfering RNA (siRNA) to validate the function of candidate SNORAs and SNORDs against specific viruses.
Main Results:
- Identified over 1,000 candidate host genes conferring resistance to viral infection.
- Discovered that 83 identified genes encoded small nucleolar RNAs (SNORAs and SNORDs), with most residing within introns of protein-coding genes.
- siRNA validation confirmed that eight out of nine targeted SNORAs/SNORDs enhanced cellular resistance to multiple viruses, including cowpox, Dengue, influenza, rhinovirus, herpes simplex, and respiratory syncytial virus.
Conclusions:
- Small nucleolar RNAs (SNORAs and SNORDs) are significantly involved in cellular antiviral responses and host-virus interactions.
- Disruption of SNORA/D genes can confer broad-spectrum resistance to various viral infections.
- These findings highlight SNORAs and SNORDs as potential therapeutic targets for antiviral strategies.
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