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Shue B, Chiramel AI, Cerikan B, et al. Genome-Wide CRISPR Screen Identifies RACK1 as a Critical Host Factor for Flavivirus Replication. J Virol. 2021;95(24):e0059621doi: 10.1128/JVI.00596-21.
Shue, B., Chiramel, A. I., Cerikan, B., To, T. H., Frölich, S., Pederson, S. M., Kirby, E. N., Eyre, N. S., Bartenschlager, R. F. W., Best, S. M., & Beard, M. R. (2021). Genome-Wide CRISPR Screen Identifies RACK1 as a Critical Host Factor for Flavivirus Replication. Journal of virology, 95(24), e0059621. https://doi.org/10.1128/JVI.00596-21
Shue, Byron, et al. "Genome-Wide CRISPR Screen Identifies RACK1 as a Critical Host Factor for Flavivirus Replication." Journal of virology vol. 95,24 (2021): e0059621. doi: https://doi.org/10.1128/JVI.00596-21
Shue B, Chiramel AI, Cerikan B, To TH, Frölich S, Pederson SM, Kirby EN, Eyre NS, Bartenschlager RFW, Best SM, Beard MR. Genome-Wide CRISPR Screen Identifies RACK1 as a Critical Host Factor for Flavivirus Replication. J Virol. 2021 Nov 23;95(24):e0059621. doi: 10.1128/JVI.00596-21. Epub 2021 Sep 29. PMID: 34586867; PMCID: PMC8610583.
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J Virol. 2021 Nov 23;95(24):e0059621. doi: 10.1128/JVI.00596-21. Epub 2021 Sep 29.

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

Journal of virology

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, Michael R Beard

Affiliations

  1. Research Centre for Infectious Diseases, Department of Molecular and Biomedical Science, The University of Adelaidegrid.1010.0, Adelaide, Australia.
  2. Rocky Mountain Laboratories, National Institutes of Health (NIH), Hamilton, Montana, USA.
  3. Department of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, 69120 Germany.
  4. Bioinformatics Hub, The University of Adelaidegrid.1010.0, Adelaide, Australia.

PMID: 34586867 PMCID: PMC8610583 DOI: 10.1128/JVI.00596-21

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.

Keywords: ZIKV; crispr; flavivirus; host factor; organelle; screen; viral replication

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