Evidence map›Paper›PMID 34586867›Full record

ArticleJournal of virology2021

Genome-Wide CRISPR Screen Identifies RACK1 as a Critical Host Factor for Flavivirus Replication.

Byron Shue, Abhilash I Chiramel, Berati Cerikan, Thu-Hien To, Sonja Frölich, Stephen M Pederson, Emily N Kirby, Nicholas S Eyre, Ralf F W Bartenschlager, Sonja M Best and 1 more

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
8.6field-weighted citation impact, top 2% of its field
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

44 citing papers in PubMed, 62 citations in OpenAlex.

  1. Review
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  8. Cellular Biology: Virus-Host Interactions and RNA Structure and Function.Current topics in microbiology and immunology · 2026
    Review
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  10. Review
  11. Review
  12. Article
  13. Review
  14. Functional Roles and Host Interactions ofPathogens (Basel, Switzerland) · 2025
    Review
  15. Article
  16. CBX2 suppresses interferon signaling to diminish tumor immunogenicity via a noncanonical corepressor complex.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
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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

11 authors at 3 institutions in 3 countries.

Byron ShueResearch Centre for Infectious Diseases, Department of Molecular and Biomedical Science, The University of Adelaidegrid.1010.0, Adelaide, Australia.
Abhilash I ChiramelRocky Mountain Laboratories, National Institutes of Health (NIH), Hamilton, Montana, USA.
Berati CerikanDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, 69120 Germany.
Thu-Hien ToBioinformatics Hub, The University of Adelaidegrid.1010.0, Adelaide, Australia.
Sonja FrölichResearch Centre for Infectious Diseases, Department of Molecular and Biomedical Science, The University of Adelaidegrid.1010.0, Adelaide, Australia.
Stephen M PedersonBioinformatics Hub, The University of Adelaidegrid.1010.0, Adelaide, Australia.
Emily N KirbyResearch Centre for Infectious Diseases, Department of Molecular and Biomedical Science, The University of Adelaidegrid.1010.0, Adelaide, Australia.
Nicholas S EyreResearch Centre for Infectious Diseases, Department of Molecular and Biomedical Science, The University of Adelaidegrid.1010.0, Adelaide, Australia.
Ralf F W BartenschlagerDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, 69120 Germany.ORCID 0000-0001-5601-9307
Sonja M BestRocky Mountain Laboratories, National Institutes of Health (NIH), Hamilton, Montana, USA.
Michael R BeardResearch Centre for Infectious Diseases, Department of Molecular and Biomedical Science, The University of Adelaidegrid.1010.0, Adelaide, Australia.ORCID 0000-0002-4106-1016
The University of Adelaide · AUHeidelberg University · DENational Institutes of Health · US

Funding

Department of Health | National Health and Medical Research Council (NHMRC) APP1145613
6 · The paper itself

Abstract

Cellular factors have important roles in all facets of the flavivirus replication cycle. Deciphering viral-host protein interactions is essential for understanding the flavivirus life cycle as well as development of effective antiviral strategies. To uncover novel host factors that are co-opted by multiple flaviviruses, a CRISPR/Cas9 genome wide knockout (KO) screen was employed to identify genes required for replication of Zika virus (ZIKV). Receptor for Activated Protein C Kinase 1 (RACK1) was identified as a novel host factor required for ZIKV replication, which was confirmed via complementary experiments. Depletion of RACK1 via siRNA demonstrated that RACK1 is important for replication of a wide range of mosquito- and tick-borne flaviviruses, including West Nile Virus (WNV), Dengue Virus (DENV), Powassan Virus (POWV) and Langat Virus (LGTV) as well as the coronavirus SARS-CoV-2, but not for YFV, EBOV, VSV or HSV. Notably, flavivirus replication was only abrogated when RACK1 expression was dampened prior to infection. Utilising a non-replicative flavivirus model, we show altered morphology of viral replication factories and reduced formation of vesicle packets (VPs) in cells lacking RACK1 expression. In addition, RACK1 interacted with NS1 protein from multiple flaviviruses; a key protein for replication complex formation. Overall, these findings reveal RACK1's crucial role to the biogenesis of pan-flavivirus replication organelles.

Indexed as

CRISPR-Cas SystemsVirus ReplicationA549 CellsAedesAnimalsChlorocebus aethiopsCOVID-19CulicidaeDengue VirusFlavivirusGenome-Wide Association StudyHEK293 CellsHost-Pathogen InteractionsHumansNeoplasm ProteinsReceptors for Activated C KinaseNeoplasm ProteinsRACK1 protein, humanReceptors for Activated C KinaseRNA, Small InterferingRNA, Viralcrisprflavivirushost factororganellescreenviral replicationZIKV

Identifiers

PMID34586867
PMCPMC8610583
OpenAlexW3203929246

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.