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CRISPR Screen Reveals PACT as a Pro-Viral Factor for Dengue Viral Replication
Shwetha Shivaprasad1,2, Wenjie Qiao1, Kuo-Feng Weng1
1Department of Microbiology & Immunology, Stanford University SOM, Stanford, CA 94305, USA.
Viruses
|May 25, 2024
Summary
Researchers discovered that the Protein Activator of Interferon-Induced Protein Kinase (PACT) surprisingly promotes dengue virus (DENV) replication. This finding offers new avenues for developing host-directed antiviral therapies against DENV infection.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Dengue virus (DENV) infects millions globally, with no current antivirals.
- CRISPR screening identifies host factors crucial for viral infection and potential therapeutic targets.
Purpose of the Study:
- To identify host factors essential for DENV infection using CRISPR screening.
- To elucidate the role of Protein Activator of Interferon-Induced Protein Kinase (PACT) in DENV replication.
Main Methods:
- Focused CRISPR library screen in human Huh7 cells.
- Analysis of DENV RNA and protein levels after PACT knockout and re-expression.
- Global gene expression analysis to identify affected pathways.
Main Results:
- PACT was identified as a novel pro-viral factor for DENV.
- PACT knockout significantly reduced DENV RNA and protein levels.
- PACT knockout prevented upregulation of specific ER-associated pro-viral genes in DENV-infected cells.
Conclusions:
- PACT plays a pro-viral role in DENV infection, promoting viral RNA replication.
- PACT may modulate DENV replication through ER-associated pro-viral gene expression.
- PACT represents a potential target for host-directed dengue antiviral strategies.
