The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
A CRISPR screen defines a signal peptide processing pathway required by flaviviruses
Open accessAbstract
Flaviviruses infect hundreds of millions of people annually, and no antiviral therapy is available. We performed a genome-wide CRISPR/Cas9-based screen to identify host genes that, when edited, resulted in reduced flavivirus infection. Here, we validated nine human genes required for flavivirus infectivity, and these were associated with endoplasmic reticulum functions including translocation, protein degradation, and N-linked glycosylation. In particular, a subset of endoplasmic reticulum-associated signal peptidase complex (SPCS) proteins was necessary for proper cleavage of the flavivirus structural proteins (prM and E) and secretion of viral particles. Loss of SPCS1 expression resulted in markedly reduced yield of all Flaviviridae family members tested (West Nile, dengue, Zika, yellow fever, Japanese encephalitis, and hepatitis C viruses), but had little impact on alphavirus, bunyavirus, or rhabdovirus infection or the surface expression or secretion of diverse host proteins. We found that SPCS1 dependence could be bypassed by replacing the native prM protein leader sequences with a class I major histocompatibility complex (MHC) antigen leader sequence. Thus, SPCS1, either directly or indirectly via its interactions with host proteins, preferentially promotes the processing of specific protein cargo, and Flaviviridae have a unique dependence on this signal peptide processing pathway. SPCS1 and other signal processing pathway members could represent pharmacological targets for inhibiting infection by the expanding number of flaviviruses of medical concern.
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Cites
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
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Multiplex Genome Engineering Using CRISPR/Cas Systems
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Genome-scale CRISPR-Cas9 knockout screening in human cells
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Cited by
Genome-scale CRISPR-Cas9 Knockout and Transcriptional Activation Screening
Joung, J., Konermann, S., Gootenberg, J. S., Abudayyeh, O. O., Platt, R. J., Brigham, M. D., Sanjana, N. E., & Zhang, F. (2017) · Nature Protocols · doi:10.1038/nprot.2017.016 · Cited by 1,243
Delivering CRISPR: a review of the challenges and approaches
Lino, C. A., Harper, J. C., Carney, J. P., & Timlin, J. A. (2018) · Drug Delivery · doi:10.1080/10717544.2018.1474964 · Cited by 1,185
Pooled CRISPR screening with single-cell transcriptome readout.
Datlinger, P., Rendeiro, A. F., Schmidl, C., Krausgruber, T., Traxler, P., Klughammer, J., Schuster, L. C., Kuchler, A., Alpar, D., & Bock, C. (2017) · Nature Methods · doi:10.1038/nmeth.4177 · Cited by 1,096
Am I ready for CRISPR? A user's guide to genetic screens
Doench, J. G. (2018) · Nature Reviews Genetics · doi:10.1038/nrg.2017.97 · Cited by 452
Rewiring cellular networks by members of the Flaviviridae family
Neufeldt, C. J., Cortese, M., Acosta, E. G., & Bartenschlager, R. (2018) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2017.170 · Cited by 409
Metadata
- Authors
- Zhang, R., Miner, J. J., Gorman, M. J., Rausch, K., Ramage, H., White, J. P., Zuiani, A., Zhang, P., Fernandez, E., Zhang, Q., Dowd, K. A., Pierson, T. C., Cherry, S., & Diamond, M. S.
- Venue
- Nature
- Published
- 2016-06-17
- Volume
- 535
- Issue
- 7610
- Pages
- 164-168
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2426204902
- Cited by
- 369
- References
- 40
- FWCI
- 50.78
- Type
- journal article
- Language
- en
- Open access
- green
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- Zhang, R., Miner, J. J., Gorman, M. J., Rausch, K., Ramage, H., White, J. P., Zuiani, A., Zhang, P., Fernandez, E., Zhang, Q., Dowd, K. A., Pierson, T. C., Cherry, S., & Diamond, M. S. (2016). A CRISPR screen defines a signal peptide processing pathway required by flaviviruses. Nature. https://doi.org/10.1038/nature18625
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