Rhinovirus Uses a Phosphatidylinositol 4-Phosphate/Cholesterol Counter-Current for the Formation of Replication Compartments at the ER-Golgi Interface

Roulin, Pascal; Lötzerich, Mark; Torta, Federico; Tanner, Lukas B.; Kuppeveld, Frank J. M. van; Wenk, Markus R.; Greber, Urs F.

doi:10.1016/j.chom.2014.10.003

Cited by 193 publications

(259 citation statements)

References 46 publications

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“…Fatty acid synthase encoded by FASN is required for CVB3 replication (Wilsky et al 2012). OSBP and SACM1L are required for sterol/PI(4)P exchange at the ERGolgi interface, and rhinovirus and enterovirus, which belong to Picornaviridae like CVB3, use these processes for viral replication (Mesmin et al 2013;Roulin et al 2014;Strating et al 2015). Our screening results are in agreement with these previous reports and give us confidence in our approach.…”

Section: Dnm2 Fasn Osbp and Sacm1l Are Known To Be Important For Esupporting

confidence: 90%

Arrayed CRISPR screen with image-based assay reliably uncovers host genes required for coxsackievirus infection

Lee

Kim

et al. 2018

Genome Res.

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Pooled CRISPR screens based on lentiviral systems have been widely applied to identify the effect of gene knockout on cellular phenotype. Although many screens were successful, they also have the limitation that genes conferring mild phenotypes or those essential for growth can be overlooked, as every genetic perturbation is incorporated in the same population. Arrayed screens, on the other hand, incorporate a single genetic perturbation in each well and could overcome these limitations. However, arrayed screens based on siRNA-mediated knockdown were recently criticized for low reproducibility caused by incomplete inhibition of gene expression. To overcome these limitations, we developed a novel arrayed CRISPR screen based on a plasmid library expressing a single guide RNA (sgRNA) and disrupted 1514 genes, encoding kinases, proteins related to endocytosis, and Golgi-localized proteins, individually using 4542 sgRNAs (three sgRNAs per gene). This screen revealed host factors required for infection by coxsackievirus B3 (CVB3) from Picornaviridae, which includes human pathogens causing diverse diseases. Many host factors that had been overlooked in a conventional pooled screen were identified for CVB3 infection, including entry-related factors, translational initiation factors, and several replication factors with different functions, demonstrating the advantage of the arrayed screen. This screen was quite reliable and reproducible, as most genes identified in the primary screen were confirmed in secondary screens. Moreover, ACBD3, whose phenotype was not affected by siRNA-mediated knockdown, was reliably identified. We propose that arrayed CRISPR screens based on sgRNA plasmid libraries are powerful tools for arrayed genetic screening and applicable to larger-scale screens.

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Section: Dnm2 Fasn Osbp and Sacm1l Are Known To Be Important For Esupporting

confidence: 90%

Arrayed CRISPR screen with image-based assay reliably uncovers host genes required for coxsackievirus infection

Lee

Kim

et al. 2018

Genome Res.

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“…5A). Cross-resistance of the 3A[H57Y] mutant to PI4KIIIb inhibitors and OSW-1 suggests that PI4KIIIb and OSBP act in the same pathway and is in line with previous reports that OSBP is recruited by PI4KIIIb-generated PI4P (Arita, 2014;Arita et al, 2013;Roulin et al, 2014).…”

Section: Introductionsupporting

confidence: 90%

“…Replication organelles of enteroviruses are enriched in PI4P lipids produced by PI4KIIIb (Hsu et al, 2010). Recently, oxysterol-binding protein (OSBP), a PI4P-binding protein that shuttles cholesterol between membrane compartments, was implicated as another host factor for enterovirus replication (Arita, 2014;Arita et al, 2013;Roulin et al, 2014;Wang et al, 2014). Fig.…”

Section: Introductionmentioning

confidence: 99%

Broad-range inhibition of enterovirus replication by OSW-1, a natural compound targeting OSBP

et al. 2015

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Enteroviruses, e.g., polio-, coxsackie-and rhinoviruses, constitute a large genus within the Picornaviridae family of positive-strand RNA viruses and include many important pathogens linked to a variety of acute and chronic diseases. Despite their huge medical and economic impact, no approved antiviral therapy is yet available. Recently, the oxysterol-binding protein (OSBP) was implicated as a host factor for enterovirus replication. Here, we investigated the antiviral activity of the natural compound OSW-1, a ligand of OSBP that is under investigation as an anti-cancer drug. OSW-1 potently inhibited the replication of all enteroviruses tested, with IC50 values in the low nanomolar range, acted at the genome replication stage and was effective in all tested cell types of three different species. Importantly, OSBP overexpression rescued viral replication, demonstrating that the antiviral effect of OSW-1 is due to targeting OSBP. Together, we here report the anti-enterovirus activity of the natural anti-cancer compound OSW-1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 Enteroviruses form a large genus belonging to the Picornaviridae family of positive-strand RNA viruses [(+)RNA] and include important human pathogens. Enteroviral infections have been implicated in a number of acute and chronic diseases, ranging from poliomyelitis (poliovirus), meningoencephalitis and myocarditis (coxsackieviruses and echoviruses), and common cold to asthma exacerbation and chronic obstructive pulmonary disease (rhinoviruses). Poliovirus is the only member of the genus for which an efficient vaccine is available and no antiviral therapy is currently approved for treating enteroviral infections. OSW-1 is a natural compound extracted from the bulbs of the plant Ornithogalum saundersiae that has been studied mainly for its anti-cancer activity. Burgett et al. (2011) identified OSBP as a high-affinity target of OSW-1 using affinity chromatography and demonstrated that OSW-1 exerts its anti-cancer activity via OSBP.In this study, we investigated the antiviral activity of OSW-1. We assessed the effect of OSW-1 on a single-round of infection of HeLa or Buffalo Green Monkey (BGM) kidney cells by viruses from different species in the Enterovirus genus, i.e., enterovirus 71 (EV71, enterovirus A species), coxsackievirus A21 (CVA21, enterovirus C species), human rhinovirus 2 (HRV2, rhinovirus A species) and human rhinovirus 14 (HRV-14, rhinovirus B species). All enteroviruses tested were sensitive to OSW-1, with IC50 values ranging between 2.4 and 9.4 nM ( Fig. 1A-E). Cell viability assays performed in parallel revealed no cytotoxicity (CC50 > 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 ...

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“…5H to J). This result was in agreement with the notion that GCA blocks the replication of HRV-related enteroviruses by dis- sociating Arf1 and COP-I from Golgi apparatus membranes (53) and that HRV-A1A requires lipid flux between the ER and Golgi apparatus for replication (54).…”

Section: Inhibition Of Gbf-1 Enhances Postentry Steps In Hadv Infectionsupporting

confidence: 91%

Chemical Induction of Unfolded Protein Response Enhances Cancer Cell Killing through Lytic Virus Infection

Bartenschlager

Suomalainen

Pennauer

et al. 2014

J Virol

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Cancer cells are susceptible to oncolytic viruses, albeit variably. Human adenoviruses (HAdVs) are widely used oncolytic agents that have been engineered to produce progeny within the tumor and elicit bystander effects. We searched for host factors enhancing bystander effects and conducted a targeted RNA interference screen against guanine nucleotide exchange factors (GEFs) of small GTPases. We show that the unfolded protein response (UPR), which is readily inducible in aggressive tumor cells, enhances melanoma or epithelial cancer cell killing upon HAdV infection. UPR was triggered by knockdown of Golgi-specific brefeldin A-resistant guanine nucleotide exchange factor 1 (GBF-1) or the GBF-1 inhibitor golgicide A (GCA) and stimulated HAdV infection. GBF-1 is a GEF for ADP ribosylation factors (Arfs) regulating endoplasmic reticulum (

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Rhinovirus Uses a Phosphatidylinositol 4-Phosphate/Cholesterol Counter-Current for the Formation of Replication Compartments at the ER-Golgi Interface

Cited by 193 publications

References 46 publications

Arrayed CRISPR screen with image-based assay reliably uncovers host genes required for coxsackievirus infection

Arrayed CRISPR screen with image-based assay reliably uncovers host genes required for coxsackievirus infection

Broad-range inhibition of enterovirus replication by OSW-1, a natural compound targeting OSBP

Chemical Induction of Unfolded Protein Response Enhances Cancer Cell Killing through Lytic Virus Infection

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