title: The interactomes of influenza virus NS1 and NS2 proteins identify new host factors and provide insights for ADAR1 playing a supportive role in virus replication.
abstract: Influenza A NS1 and NS2 proteins are encoded by the RNA segment 8 of the viral genome. NS1 is a multifunctional protein and a virulence factor while NS2 is involved in nuclear export of viral ribonucleoprotein complexes. A yeast two-hybrid screening strategy was used to identify host factors supporting NS1 and NS2 functions. More than 560 interactions between 79 cellular proteins and NS1 and NS2 proteins from 9 different influenza virus strains have been identified. These interacting proteins are potentially involved in each step of the infectious process and their contribution to viral replication was tested by RNA interference. Validation of the relevance of these host cell proteins for the viral replication cycle revealed that 7 of the 79 NS1 and/or NS2-interacting proteins positively or negatively controlled virus replication. One of the main factors targeted by NS1 of all virus strains was double-stranded RNA binding domain protein family. In particular, adenosine deaminase acting on RNA 1 (ADAR1) appeared as a pro-viral host factor whose expression is necessary for optimal viral protein synthesis and replication. Surprisingly, ADAR1 also appeared as a pro-viral host factor for dengue virus replication and directly interacted with the viral NS3 protein. ADAR1 editing activity was enhanced by both viruses through dengue virus NS3 and influenza virus NS1 proteins, suggesting a similar virus-host co-evolution.
authors.affiliation: Hospices Civils de Lyon, Hôpital de la Croix Rousse, Laboratory of Virology, Lyon, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: de Chassey
authors.forename: Anne
authors.initials: A
authors.lastname: Aublin-Gex
authors.forename: Alessia
authors.initials: A
authors.lastname: Ruggieri
authors.forename: Laurène
authors.initials: L
authors.lastname: Meyniel-Schicklin
authors.forename: Fabrine
authors.initials: F
authors.lastname: Pradezynski
authors.forename: Nathalie
authors.initials: N
authors.lastname: Davoust
authors.forename: Thibault
authors.initials: T
authors.lastname: Chantier
authors.forename: Lionel
authors.initials: L
authors.lastname: Tafforeau
authors.forename: Philippe-Emmanuel
authors.initials: PE
authors.lastname: Mangeot
authors.forename: Claire
authors.initials: C
authors.lastname: Ciancia
authors.forename: Laure
authors.initials: L
authors.lastname: Perrin-Cocon
authors.forename: Ralf
authors.initials: R
authors.lastname: Bartenschlager
authors.forename: Patrice
authors.initials: P
authors.lastname: André
authors.forename: Vincent
authors.initials: V
authors.lastname: Lotteau
mesh_terms: D000243:Adenosine Deaminase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D002460:Cell Line; D003716:Dengue Virus / Q000201:enzymology; D054884:Host-Pathogen Interactions; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology; D009980:Influenza A virus / Q000502:physiology*; D007251:Influenza, Human / Q000378:metabolism / Q000473:pathology / Q000821:virology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D020545:Respiratory Mucosa / Q000378:metabolism / Q000473:pathology / Q000821:virology; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D020798:Two-Hybrid System Techniques; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication; D000085242:Viral Proteases
chemical_list: D000243:Adenosine Deaminase; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D012261:Ribonucleoproteins; D012697:Serine Endopeptidases; D017361:Viral Nonstructural Proteins; D037521:Virulence Factors; C085820:INS1 protein, influenza virus; C556232:NS2 protein, influenza virus A; C504449:NS3 protease, dengue virus; D000085242:Viral Proteases; C567955:ADARB1 protein, human