Evidence map›Paper›PMID 38793607›Full record

ArticleViruses2024

CRISPR Screen Reveals PACT as a Pro-Viral Factor for Dengue Viral Replication.

Shwetha Shivaprasad, Wenjie Qiao, Kuo-Feng Weng, Pavithra Umashankar, Jan E Carette, Peter Sarnow

Abstract read
In one paragraph

Article in Viruses, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Druggable genome screens identify SPP as an antiviral host target for multiple flaviviruses.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  6. Review
  7. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Shwetha ShivaprasadDepartment of Microbiology & Immunology, Stanford University SOM, Stanford, CA 94305, USA.ORCID 0000-0003-4734-6140
Wenjie QiaoDepartment of Microbiology & Immunology, Stanford University SOM, Stanford, CA 94305, USA.
Kuo-Feng WengDepartment of Microbiology & Immunology, Stanford University SOM, Stanford, CA 94305, USA.
Pavithra UmashankarMolecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bengaluru 560064, Karnataka, India.ORCID 0009-0008-6720-5648
Jan E CaretteDepartment of Microbiology & Immunology, Stanford University SOM, Stanford, CA 94305, USA.
Peter SarnowDepartment of Microbiology & Immunology, Stanford University SOM, Stanford, CA 94305, USA.ORCID 0000-0002-2043-2770

Funding

Roles for microRNA-122 in hepatitis C virus RNA amplificationR01AI069000 · NIAID · STANFORD UNIVERSITY · PI SARNOW, PETER · 2006 to 2022
$6.2M
Host Genes Critical for Flavivirus InfectionR01AI141970 · NIAID · STANFORD UNIVERSITY · PI CARETTE, JAN E · 2019 to 2023
$2.0M
Department of Science and Technology SERB/2023/01976Jawaharlal Nehru Centre for Advanced Scientific Research JNC/2023/02064NIAID NIH HHS R01 AI141970NIH HHS R01 AI069000 (to P.S.), R01 AI140186 (to J.E.C.); NIH R01 AI141970 (to J.E.C.); NIH R01 AI130123 (to J.E.C.)
6 · The paper itself

Abstract

The dengue virus is a single-stranded, positive-sense RNA virus that infects ~400 million people worldwide. Currently, there are no approved antivirals available. CRISPR-based screening methods have greatly accelerated the discovery of host factors that are essential for DENV infection and that can be targeted in host-directed antiviral interventions. In the present study, we performed a focused CRISPR (Clustered Regularly Interspaced Palindromic Repeats) library screen to discover the key host factors that are essential for DENV infection in human Huh7 cells and identified the Protein Activator of Interferon-Induced Protein Kinase (PACT) as a novel pro-viral factor for DENV. PACT is a double-stranded RNA-binding protein generally known to activate antiviral responses in virus-infected cells and block viral replication. However, in our studies, we observed that PACT plays a pro-viral role in DENV infection and specifically promotes viral RNA replication. Knockout of PACT resulted in a significant decrease in DENV RNA and protein abundances in infected cells, which was rescued upon ectopic expression of full-length PACT. An analysis of global gene expression changes indicated that several ER-associated pro-viral genes such as ERN1, DDIT3, HERPUD1, and EIF2AK3 are not upregulated in DENV-infected PACT knockout cells as compared to infected wildtype cells. Thus, our study demonstrates a novel role for PACT in promoting DENV replication, possibly through modulating the expression of ER-associated pro-viral genes.

Indexed as

CRISPR-Cas SystemsDengue VirusHost-Pathogen InteractionsRNA-Binding ProteinsVirus ReplicationCell LineDengueHumansRNA, ViralRNA-Binding ProteinsRNA, ViralCRISPR screendengue virushost–virus interactions

Identifiers

PMID38793607
PMCPMC11125577

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.