Open Access Highly Accessed Research article

Flavivirus NS3 and NS5 proteins interaction network: a high-throughput yeast two-hybrid screen

Marc Le Breton12, Laurène Meyniel-Schicklin12, Alexandre Deloire12, Bruno Coutard3, Bruno Canard3, Xavier de Lamballerie4, Patrice Andre125, Chantal Rabourdin-Combe12, Vincent Lotteau12 and Nathalie Davoust126*

Author Affiliations

1 Inserm Unit 851, Lyon, France

2 Université de Lyon, SFR BioSciences Gerland-Lyon Sud, Lyon, France

3 Architecture et Fonction des Macromolécules Biologiques, CNRS and Universités d'Aix-Marseille I et II, UMR 6098, Marseille, France

4 UMR190, IRD and Université d'Aix Marseille II, Marseille, France

5 Hospices Civils de Lyon, Hôpital de la Croix-Rousse, Laboratoire de virologie, Lyon, France

6 Ecole Normale Supérieure de Lyon, Lyon, France

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BMC Microbiology 2011, 11:234  doi:10.1186/1471-2180-11-234

Published: 20 October 2011



The genus Flavivirus encompasses more than 50 distinct species of arthropod-borne viruses, including several major human pathogens, such as West Nile virus, yellow fever virus, Japanese encephalitis virus and the four serotypes of dengue viruses (DENV type 1-4). Each year, flaviviruses cause more than 100 million infections worldwide, some of which lead to life-threatening conditions such as encephalitis or haemorrhagic fever. Among the viral proteins, NS3 and NS5 proteins constitute the major enzymatic components of the viral replication complex and are essential to the flavivirus life cycle.


We report here the results of a high-throughput yeast two-hybrid screen to identify the interactions between human host proteins and the flavivirus NS3 and NS5 proteins. Using our screen results and literature curation, we performed a global analysis of the NS3 and NS5 cellular targets based on functional annotation with the Gene Ontology features. We finally created the first flavivirus NS3 and NS5 proteins interaction network and analysed the topological features of this network. Our proteome mapping screen identified 108 human proteins interacting with NS3 or NS5 proteins or both. The global analysis of the cellular targets revealed the enrichment of host proteins involved in RNA binding, transcription regulation, vesicular transport or innate immune response regulation.


We proposed that the selective disruption of these newly identified host/virus interactions could represent a novel and attractive therapeutic strategy in treating flavivirus infections. Our virus-host interaction map provides a basis to unravel fundamental processes about flavivirus subversion of the host replication machinery and/or immune defence strategy.