ArticleNature2016
A CRISPR screen defines a signal peptide processing pathway required by flaviviruses.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 254 papers.
What it found
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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.
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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.
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Who cites it
254 citing papers in PubMed, 379 citations in OpenAlex.
- Dengue virus infection.Nature reviews. Disease primers · 2026Review
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- The Sigma1 ER membrane receptor promotes structural protein folding and genome packaging of dengue virus.PLoS pathogens · 2026Article
- Zika virus recruits karyopherin α6 for efficient replication via NS2B.Journal of virology · 2026Article
- Virus-host interactome reveals host cellular pathways perturbed by tick-borne encephalitis virus infection.iScience · 2026Article
- Human interferon stimulated genes target ancient features of animal and bacterial viral replication.bioRxiv : the preprint server for biology · 2026Article
- Annotating genomes at increased scale and resolution.Nature reviews. Genetics · 2026Review
- Dissecting the host determinants of orthoflavivirus infection using QIC-seq.PLoS pathogens · 2026Article
- Structural basis of signal peptide recognition by the signal peptidase complex.Nature communications · 2026Article
- Genome-wide CRISPR knockout cell screening platform for the disease vector tick speciesbioRxiv : the preprint server for biology · 2026Article
- SPCS2 serves as a critical host factor for JEV replication by regulating viral protein stability and virion assembly.Microbiology spectrum · 2026Article
- Signal peptidase complex mediates rotavirus VP7 processing and virion assembly.PLoS pathogens · 2026Article
- Article
- Multiomics Analysis of Arboviral Capsid Targets in Mosquitoes Reveals a Proviral Function of the Chromatin-Remodeling Brahma Complex.Molecular & cellular proteomics : MCP · 2026Article
- Affinity-based protein profiling of the antiviral natural product nanchangmycin.RSC chemical biology · 2026Article
- Cellular Biology: Virus-Host Interactions and RNA Structure and Function.Current topics in microbiology and immunology · 2026Review
- Meta-analysis of functional genomics studies reveals conserved cellular pathways required by viruses of pandemic concern.Access microbiology · 2026Article
- Genome-wide CRISPR screen identifies RNF24 as a critical host factor for foot-and-mouth disease virus entry.Frontiers in cell and developmental biology · 2026Article
- Replicon-based genome-wide CRISPR knockout screening for the identification of host factors involved in viral replication.Nature communications · 2025Article
- Signal peptidase complex mediates rotavirus VP7 processing and virion assembly.bioRxiv : the preprint server for biology · 2025Article
194 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
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 unknown 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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Registered trials
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.