Inducible CRISPR activation screen for interferon-stimulated genes identifies OAS1 as a SARS-CoV-2 restriction factor

Danziger, Oded; Patel, Roosheel; DeGrace, Emma J; Rosen, Mikaela R; Rosenberg, Brad R.

doi:10.1371/journal.ppat.1010464

Cited by 38 publications

(37 citation statements)

References 115 publications

(170 reference statements)

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“…Most antiviral resistance factors are Interferon Stimulated Genes (ISGs), in other words, genes that activate their expression after detecting interferons by cellular receptors (Schneider et al, 2014;Danziger et al, 2022). Binding interferon to their receptors triggers a series of signaling cascade in the cell to protect against an infection.…”

Section: Resistance Susceptibility and Permissibilitymentioning

confidence: 99%

“…Binding interferon to their receptors triggers a series of signaling cascade in the cell to protect against an infection. ISGs encode functionally diverse gene products, including the antiviral effectors that antagonise distinct steps of viral life cycles (Schoggins, 2019;Danziger et al, 2022). As they depend on an interferon stimulus, induced resistance usually is not a concern for in vitro virology studies, as most cell lines used for viral production do not produce endogenous interferons.…”

Section: Resistance Susceptibility and Permissibilitymentioning

confidence: 99%

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Choosing a cellular model to study SARS-CoV-2

Souza

Bideau

Boschi

et al. 2022

Front. Cell. Infect. Microbiol.

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As new pathogens emerge, new challenges must be faced. This is no different in infectious disease research, where identifying the best tools available in laboratories to conduct an investigation can, at least initially, be particularly complicated. However, in the context of an emerging virus, such as SARS-CoV-2, which was recently detected in China and has become a global threat to healthcare systems, developing models of infection and pathogenesis is urgently required. Cell-based approaches are crucial to understanding coronavirus infection biology, growth kinetics, and tropism. Usually, laboratory cell lines are the first line in experimental models to study viral pathogenicity and perform assays aimed at screening antiviral compounds which are efficient at blocking the replication of emerging viruses, saving time and resources, reducing the use of experimental animals. However, determining the ideal cell type can be challenging, especially when several researchers have to adapt their studies to specific requirements. This review strives to guide scientists who are venturing into studying SARS-CoV-2 and help them choose the right cellular models. It revisits basic concepts of virology and presents the currently available in vitro models, their advantages and disadvantages, and the known consequences of each choice.

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Section: Resistance Susceptibility and Permissibilitymentioning

confidence: 99%

Section: Resistance Susceptibility and Permissibilitymentioning

confidence: 99%

Choosing a cellular model to study SARS-CoV-2

Souza

Bideau

Boschi

et al. 2022

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

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“…There are three OAS family proteins (OAS1, OAS2, OAS3) present in humans. A recent report using a CRISPR activation screen identified OAS1 as a major antiviral factor in restricting SARS-CoV-2 infection [ 23 ]. Notably, in this CRISPRa screening study [ 23 ], OAS2 and OAS3 were not identified to have an antiviral role.…”

Section: Resultsmentioning

confidence: 99%

“…A recent report using a CRISPR activation screen identified OAS1 as a major antiviral factor in restricting SARS-CoV-2 infection [ 23 ]. Notably, in this CRISPRa screening study [ 23 ], OAS2 and OAS3 were not identified to have an antiviral role. However, in our study, we found that all three OAS genes—OAS1, OAS2 and OAS3—were induced in severe COVID-19 samples and may have implications on host response to COVID-19 ( Figure 1 D,E).…”

Section: Resultsmentioning

confidence: 99%

Comparative Upper Respiratory Tract Transcriptomic Profiling Reveals a Potential Role of Early Activation of Interferon Pathway in Severe COVID-19

Bhat

Shibata

Leong

et al. 2022

Viruses

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Infection with SARS-CoV-2 results in Coronavirus disease 2019 (COVID-19) is known to cause mild to acute respiratory infection and sometimes progress towards respiratory failure and death. The mechanisms driving the progression of the disease and accumulation of high viral load in the lungs without initial symptoms remain elusive. In this study, we evaluated the upper respiratory tract host transcriptional response in COVID-19 patients with mild to severe symptoms and compared it with the control COVID-19 negative group using RNA-sequencing (RNA-Seq). Our results reveal an upregulated early type I interferon response in severe COVID-19 patients as compared to mild or negative COVID-19 patients. Moreover, severely symptomatic patients have pronounced induction of interferon stimulated genes (ISGs), particularly the oligoadenylate synthetase (OAS) family of genes. Our results are in concurrence with other studies depicting the early induction of IFN-I response in severe COVID-19 patients, providing novel insights about the ISGs involved.

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“…This enzyme synthesizes oligomers that activate RNAse L, which degrades cellular and viral RNA and impairs viral replication [ 70 ]. Danziger et al found that OAS1 catalytic activity is required for antiviral response against SARS-CoV-2 [ 71 ]. Moreover, a membrane-associated OAS1 form could act as a ds-RNA sensor in infection sites.…”

Section: Discussionmentioning

confidence: 99%

Pin-Pointing the Key Hubs in the IFN-γ Pathway Responding to SARS-CoV-2 Infection

Toro

Lage-Vickers

Bizzotto

et al. 2022

Viruses

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Interferon gamma (IFN-γ) may be potential adjuvant immunotherapy for COVID-19 patients. In this work, we assessed gene expression profiles associated with the IFN-γ pathway in response to SARS-CoV-2 infection. Employing a case-control study from SARS-CoV-2-positive and -negative patients, we identified IFN-γ-associated pathways to be enriched in positive patients. Bioinformatics analyses showed upregulation of MAP2K6, CBL, RUNX3, STAT1, and JAK2 in COVID-19-positive vs. -negative patients. A positive correlation was observed between STAT1/JAK2, which varied alongside the patient’s viral load. Expression of MX1, MX2, ISG15, and OAS1 (four well-known IFN-stimulated genes (ISGs)) displayed upregulation in COVID-19-positive vs. -negative patients. Integrative analyses showcased higher levels of ISGs, which were associated with increased viral load and STAT1/JAK2 expression. Confirmation of ISGs up-regulation was performed in vitro using the A549 lung cell line treated with Poly (I:C), a synthetic analog of viral double-stranded RNA; and in different pulmonary human cell lines and ferret tracheal biopsies infected with SARS-CoV-2. A pre-clinical murine model of Coronavirus infection confirmed findings displaying increased ISGs in the liver and lungs from infected mice. Altogether, these results demonstrate the role of IFN-γ and ISGs in response to SARS-CoV-2 infection, highlighting alternative druggable targets that can boost the host response.

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Inducible CRISPR activation screen for interferon-stimulated genes identifies OAS1 as a SARS-CoV-2 restriction factor

Cited by 38 publications

References 115 publications

Choosing a cellular model to study SARS-CoV-2

Choosing a cellular model to study SARS-CoV-2

Comparative Upper Respiratory Tract Transcriptomic Profiling Reveals a Potential Role of Early Activation of Interferon Pathway in Severe COVID-19

Pin-Pointing the Key Hubs in the IFN-γ Pathway Responding to SARS-CoV-2 Infection

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