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Detecting host factors involved in virus infection by observing the clustering of infected cells in siRNA screening images

Apichat Suratanee, Ilka Rebhan, Petr Matula, Anil Kumar, Lars Kaderali, Karl Rohr, Ralf Bartenschlager, Roland Eils, Rainer König
2010 Computer applications in the biosciences : CABIOS  
Results: Viral infection is mainly spread by cell-cell contacts and clustering of infected cells can be observed during spreading of the infection in situ and in vivo.  ...  Conclusion: We report of an alternative method for high-throughput imaging methods to detect host factors being relevant for the infection efficiency of viruses.  ...  Conflict of Interest: none declared.  ... 
doi:10.1093/bioinformatics/btq398 pmid:20823335 pmcid:PMC2935410 fatcat:zk4dd3czj5hz3ondguq53m23ou

A genome-wide genetic screen for host factors required for hepatitis C virus propagation

Q. Li, A. L. Brass, A. Ng, Z. Hu, R. J. Xavier, T. J. Liang, S. J. Elledge
2009 Proceedings of the National Academy of Sciences of the United States of America  
We applied a two-part screening protocol to allow identification of host factors involved in the complete viral lifecycle.  ...  To find host factors required by HCV, we completed a genome-wide small interfering RNA (siRNA) screen using an infectious HCV cell culture system.  ...  To find host factors involved in later stages of viral infection, we undertook part two of the screen, by exposing fresh Huh 7.5.1 cells to culture supernatant from part one for 48 h, then detecting core  ... 
doi:10.1073/pnas.0907439106 pmid:19717417 pmcid:PMC2752535 fatcat:ekxc47epcvdl3oc2bwdhhw5qnq

Large Scale RNAi Reveals the Requirement of Nuclear Envelope Breakdown for Nuclear Import of Human Papillomaviruses

Inci Aydin, Susanne Weber, Berend Snijder, Pilar Samperio Ventayol, Andreas Kühbacher, Miriam Becker, Patricia M. Day, John T. Schiller, Michael Kann, Lucas Pelkmans, Ari Helenius, Mario Schelhaas (+1 others)
2014 PLoS Pathogens  
The results accentuate the value of genes found by RNAi screens for investigation of viral infections.  ...  The list of cell functions required during HPV16 infection will, moreover, provide a resource for future virus-host cell interaction studies.  ...  Thompson (LCO, NIH) for assistance in pseudovirus production. We are also grateful for the help of C. Meyers and J. Biryukov (Penn State University) to set up the production of raft-derived HPV16.  ... 
doi:10.1371/journal.ppat.1004162 pmid:24874089 pmcid:PMC4038628 fatcat:2xmuyx46cvb3bhj2j7vhwvt4wu

Illuminating the host - How RNAi screens shed light on host-pathogen interactions

Miguel Prudêncio, Maik J. Lehmann
2009 Biotechnology Journal  
This review describes recent progress in RNAi screening approaches, highlighting both the limitations and the tremendous potential of RNAi-based screens for the identification of essential host cell factors  ...  Improvements in gene knockdown studies by RNA interference (RNAi) combined with recent developments in instrumentation and image analysis enable the use of high-throughput screening approaches to elucidate  ...  [61] was set up to determine host factors involved in all stages of virus infection from virus entry to release and viral cell-to-cell spread.  ... 
doi:10.1002/biot.200900071 pmid:19507150 fatcat:h3niykasorekbairw5tgejirqq

A genome wide RNA interference screening method to identify host factors that modulate Influenza A virus replication

Christopher R. Chin, Abraham L. Brass
2013 Methods  
This work describes the use of an RNAi screening method employing an immunofluorescence image-based strategy and influenza A virus.  ...  The use of genome wide RNA interference (RNAi) screens to investigate host-viral interactions has revealed unexpected connections that have improved our understanding of viral pathogenesis and cell biology  ...  Loss-of-function assay to find host proteins involved in influenza A virus infection.  ... 
doi:10.1016/j.ymeth.2012.09.009 pmid:23036328 pmcid:PMC4145670 fatcat:4tl25nsd6bcopmddp4su4pj5my

Identification of Zika Virus and Dengue Virus Dependency Factors using Functional Genomics

George Savidis, William M. McDougall, Paul Meraner, Jill M. Perreira, Jocelyn M. Portmann, Gaia Trincucci, Sinu P. John, Aaron M. Aker, Nicholas Renzette, Douglas R. Robbins, Zhiru Guo, Sharone Green (+2 others)
2016 Cell Reports  
Graphical Abstract Highlights d RNAi and CRISPR/Cas9 screens were used to find flavivirus dependencies d The screens recovered host factors involved in endocytosis and heparin sulfation d The EMC is required  ...  The screens recovered the ZIKV entry factor AXL as well as multiple host factors involved in endocytosis (RAB5C and RABGEF), heparin sulfation (NDST1 and EXT1), and transmembrane protein processing and  ...  Overlap with Flaviviral Screens siRNA screens for both WNV and YFV host factors in human cells, as well as a Drosophila cell-based siRNA screen for DENV host factors, have been previously published (Krishnan  ... 
doi:10.1016/j.celrep.2016.06.028 pmid:27342126 fatcat:kzcyze5irfditcbcvd7awi6aqy

siRNA Screen Identifies Trafficking Host Factors that Modulate Alphavirus Infection

Sheli R. Radoshitzky, Gianluca Pegoraro, Xiǎolì Chī, Lián Dǒng, Chih-Yuan Chiang, Lucas Jozwick, Jeremiah C. Clester, Christopher L. Cooper, Duane Courier, David P. Langan, Knashka Underwood, Kathleen A. Kuehl (+9 others)
2016 PLoS Pathogens  
Little is known about the repertoire of cellular factors involved in the replication of pathogenic alphaviruses.  ...  In this study, we used an RNAi-based screen to identify and validate trafficking host factors required for infection by the pathogenic VEEV and other pathogenic alphavirus relatives.  ...  The content of this publication does not necessarily reflect the views or policies of the US Department of the Army, the US Department of Defense or the US Department of Health and Human Services or of  ... 
doi:10.1371/journal.ppat.1005466 pmid:27031835 pmcid:PMC4816540 fatcat:htn4rgh3krbi5oweargxklnaey

RNAi Screening Reveals Proteasome- and Cullin3-Dependent Stages in Vaccinia Virus Infection

Jason Mercer, Berend Snijder, Raphael Sacher, Christine Burkard, Christopher Karl Ernst Bleck, Henning Stahlberg, Lucas Pelkmans, Ari Helenius
2012 Cell Reports  
A two-step, automated, high-throughput RNAi silencing screen was used to identify host cell factors required during vaccinia virus infection.  ...  The list of cell functions required during poxvirus infection will, moreover, provide a resource for future virus-host cell interaction studies and for the discovery of antivirals.  ...  J.M. is supported by an SNF Ambizione (PZ00P3_131988), L.P. by the University of Zurich, SNSF, ( RTD project InfectX, and the European Union, C.K.E.B by the SNF Sinergia  ... 
doi:10.1016/j.celrep.2012.09.003 pmid:23084750 fatcat:tzc6ldtpvff3xoyxlzyq63yjge

Single-cell analysis of population context advances RNAi screening at multiple levels

Berend Snijder, Raphael Sacher, Pauli Rämö, Prisca Liberali, Karin Mench, Nina Wolfrum, Laura Burleigh, Cameron C Scott, Monique H Verheije, Jason Mercer, Stefan Moese, Thomas Heger (+16 others)
2012 Molecular Systems Biology  
Here we study the influence of the cell population context, which determines a single cell's microenvironment, in image-based RNAi screens.  ...  We applied these methods to 45 RNA interference screens of various sizes, including 7 druggable genome and 2 genome-wide screens, analysing 17 different mammalian virus infections and four related cell  ...  Acknowledgements We acknowledge T Steiger and O Byrde from the ETH IT services for large-scale data storage and high-performance cluster computing, as well as G Csucs and A Vonderheit of the RNAi and image-based  ... 
doi:10.1038/msb.2012.9 pmid:22531119 pmcid:PMC3361004 fatcat:pyck4gbquffflhzacw4bf7qvue

Identification of Essential Filovirion-associated Host Factors by Serial Proteomic Analysis and RNAi Screen

Kevin B. Spurgers, Tim Alefantis, Brian D. Peyser, Gordon T. Ruthel, Alison A. Bergeron, Julie A. Costantino, Sven Enterlein, Krishna P. Kota, R. C. Dutch Boltz, M. Javad Aman, Vito G. DelVecchio, Sina Bavari
2010 Molecular & Cellular Proteomics  
Host proteins involved in cell adhesion, cytoskeleton, cell signaling, intracellular trafficking, membrane organization, and chaperones were identified.  ...  Notably, select siRNAs inhibited ebolavirus, but enhanced marburgvirus infection, suggesting important differences between the two viruses.  ...  Acknowledgments-We thank Jens Kuhn for a critical review of this manuscript. We thank Lian Dong for performing the qRT-PCR viral titer measurements.  ... 
doi:10.1074/mcp.m110.003418 pmid:20702783 pmcid:PMC3101857 fatcat:imd7gbka55adjfh2ods6vvrsqm

Asparagine deprivation causes a reversible inhibition of Human Cytomegalovirus acute virus replication [article]

Chen-Hsuin Lee, Samantha Griffiths, Paul Digard, Nhan T Pham, Manfred Auer, Jurgen Haas, Finn Grey
2019 biorxiv/medrxiv   pre-print
This study represents the most comprehensive siRNA screen for the identification of host factors involved in HCMV replication and identifies the non-essential amino acid, asparagine as a critical factor  ...  High throughput siRNA screens provide a systematic approach for the identification of novel host-virus interactions.  ...  PhD scholarship from the University of Edinburgh.  ... 
doi:10.1101/690016 fatcat:a7zkxy5pp5fdxddafdpp26zi3e

Recruitment and Activation of a Lipid Kinase by Hepatitis C Virus NS5A Is Essential for Integrity of the Membranous Replication Compartment

Simon Reiss, Ilka Rebhan, Perdita Backes, Ines Romero-Brey, Holger Erfle, Petr Matula, Lars Kaderali, Marion Poenisch, Hagen Blankenburg, Marie-Sophie Hiet, Thomas Longerich, Sarah Diehl (+12 others)
2011 Cell Host and Microbe  
To gain insight into host factor requirements for HCV replication, we performed a siRNA screen of the human kinome and identified 13 different kinases, including phosphatidylinositol-4 kinase III alpha  ...  Consistent with elevated levels of the PI4KIIIa product phosphatidylinositol-4-phosphate (PI4P) detected in HCV-infected cultured hepatocytes and liver tissue from chronic hepatitis C patients, the enzymatic  ...  This work was supported in part by the research program RNS/RNAi of the Landesstiftung Baden-Wü rttemberg (P-LS-RNS/30 to R.B.), a grant from the FORSYS ViroQuant project (BMBF, FKZ 0313923 to R.B. and  ... 
doi:10.1016/j.chom.2010.12.002 pmid:21238945 pmcid:PMC3433060 fatcat:lz4vnk5pmnacfozwfb2st2yhtu

Small interference RNA profiling reveals the essential role of human membrane trafficking genes in mediating the infectious entry of dengue virus

Firzan Ang, Andrew Wong, Mary Ng, Justin Chu
2010 Virology Journal  
Currently the involvements of human membrane trafficking host genes or factors that mediate the infectious cellular entry of dengue virus are not well defined.  ...  The infectious entry of DENV into Huh7 cells was shown to be potently inhibited by siRNAs targeting genes associated with clathrin-mediated endocytosis.  ...  The human isolate of dengue virus serotypes used in this study was a kind gift from the Department of Pathology, Singapore General Hospital.  ... 
doi:10.1186/1743-422x-7-24 pmid:20122152 pmcid:PMC2825209 fatcat:at6tmoxpvfh6pefpasojlm3zcq

RNA interference screen for human genes associated with West Nile virus infection

Manoj N. Krishnan, Aylwin Ng, Bindu Sukumaran, Felicia D. Gilfoy, Pradeep D. Uchil, Hameeda Sultana, Abraham L. Brass, Rachel Adametz, Melody Tsui, Feng Qian, Ruth R. Montgomery, Sima Lev (+6 others)
2008 Nature  
RNAinterference (RNAi) presents a powerful forward genetics approach to dissect virus-host cell interactions4 -6. Here we report the identification of 305 host proteins impacting WNV infection,  ...  However, our understanding of the molecular interaction of WNV (and related flaviviruses) with mammalian host cells is limited1.  ...  Acknowledgments The human genome RNAi library was made available through the support of the New England Regional Center of Excellence in Biodefense and Emerging Infectious Disease (U54AI057159).  ... 
doi:10.1038/nature07207 pmid:18690214 pmcid:PMC3136529 fatcat:vwqzqlxppfearecnevnfsm5j2a

Comparative Loss-of-Function Screens Reveal ABCE1 as an Essential Cellular Host Factor for Efficient Translation of Paramyxoviridae and Pneumoviridae

Danielle E. Anderson, Kristin Pfeffermann, So Young Kim, Bevan Sawatsky, James Pearson, Mikhail Kovtun, David L. Corcoran, Yvonne Krebs, Kristmundur Sigmundsson, Sharon F. Jamison, Zhen Zhen Joanna Yeo, Linda J. Rennick (+6 others)
2019 mBio  
To identify common host factors, we performed genome-scale siRNA screens with wild-type-derived measles, mumps, and respiratory syncytial viruses in the same cell line.  ...  In comparative genome-scale siRNA screens with wild-type-derived measles, mumps, and respiratory syncytial viruses in A549 cells, a human lung adenocarcinoma cell line, we identified vesicular transport  ...  We thank the Duke Functional Genomics Shared Resource for work related to the primary siRNA screens.  ... 
doi:10.1128/mbio.00826-19 fatcat:ubjshk22uncp3kguahnn5y2n4i
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