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World J Virol. May 12, 2013; 2(2): 18-31
Published online May 12, 2013. doi: 10.5501/wjv.v2.i2.18
High-throughput RNA interference screens integrative analysis: Towards a comprehensive understanding of the virus-host interplay
Sandeep Amberkar, Narsis A Kiani, Ralf Bartenschlager, Gualtiero Alvisi, Lars Kaderali
Sandeep Amberkar, Narsis A Kiani, Lars Kaderali, Institute for Medical Informatics and Biometry, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
Ralf Bartenschlager, Department of Molecular Virology, University of Heidelberg, 69121 Heidelberg, Germany
Gualtiero Alvisi, Department of Molecular Medicine, University of Padua, 35121 Padua, Italy
Author contributions: Amberkar S, Kiani NA and Alvisi G wrote the paper; Bartenschlager R, Alvisi G and Kaderali L revised the paper; Amberkar S, Kiani NA, Bartenschlager R, Alvisi G and Kaderali L approved the final version of the manuscript
Correspondence to: Dr. Gualtiero Alvisi, PhD, Assistant Professor, Department of Molecular Medicine, University of Padua, Via Aristide Gabelli, 63, 35121 Padua, Italy.
Telephone: +39-49-8272353 Fax: +39-49-8272355
Received: December 5, 2012
Revised: February 15, 2013
Accepted: March 15, 2013
Published online: May 12, 2013

Viruses are extremely heterogeneous entities; the size and the nature of their genetic information, as well as the strategies employed to amplify and propagate their genomes, are highly variable. However, as obligatory intracellular parasites, replication of all viruses relies on the host cell. Having co-evolved with their host for several million years, viruses have developed very sophisticated strategies to hijack cellular factors that promote virus uptake, replication, and spread. Identification of host cell factors (HCFs) required for these processes is a major challenge for researchers, but it enables the identification of new, highly selective targets for anti viral therapeutics. To this end, the establishment of platforms enabling genome-wide high-throughput RNA interference (HT-RNAi) screens has led to the identification of several key factors involved in the viral life cycle. A number of genome-wide HT-RNAi screens have been performed for major human pathogens. These studies enable first inter-viral comparisons related to HCF requirements. Although several cellular functions appear to be uniformly required for the life cycle of most viruses tested (such as the proteasome and the Golgi-mediated secretory pathways), some factors, like the lipid kinase Phosphatidylinositol 4-kinase IIIα in the case of hepatitis C virus, are selectively required for individual viruses. However, despite the amount of data available, we are still far away from a comprehensive understanding of the interplay between viruses and host factors. Major limitations towards this goal are the low sensitivity and specificity of such screens, resulting in limited overlap between different screens performed with the same virus. This review focuses on how statistical and bioinformatic analysis methods applied to HT-RNAi screens can help overcoming these issues thus increasing the reliability and impact of such studies.

Keywords: RNA interference, High-throughput, Cell population, Dependency factors, Bioinformatics, Human immunodeficiency virus, Hepatitis C virus, Dengue virus, Viral infection, Virus-host interactions