title: Mechanistic study of intertypic nucleoprotein complex formation and its inhibitory effect toward influenza A virus.
abstract: Co-infection of influenza A and B viruses (IAV and IBV) results in marked decreases in IAV replication. Multiple mechanisms have been proposed for this phenomenon. Recently, we reported that IBV nucleoprotein (BNP) alone can suppress IAV replication and proposed an inhibition model in which BNP binds IAV nucleoprotein (ANP) and disrupts IAV polymerase complexes. Here, using mutagenesis and co-immunoprecipitation, we determined the protein motifs mediating the intertypic ANP-BNP complex and showed that it specifically interferes with ANP׳s interaction with the PB2 subunit of the IAV polymerase but not with the other subunit PB1. We further demonstrated that BNP only suppresses growth of IAVs but not other RNA viruses. However, different IAV strains display varied sensitivity toward the BNP׳s inhibitory effect. Together, our data provide mechanistic insights into intertypic nucleoprotein complex formation and highlight the role of BNP as a potential broad-spectrum anti-IAV agent.
authors.affiliation: Virology and Cell Technology Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani, Thailand.
authors.forename: Jaraspim
authors.initials: J
authors.lastname: Narkpuk
authors.affiliation: Virology and Cell Technology Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani, Thailand. Electronic address: peera.jar@biotec.or.th.
authors.forename: Peera
authors.initials: P
authors.lastname: Jaru-Ampornpan
authors.affiliation: Faculty of Biotechnology, Atma Jaya Catholic University of Indonesia, Jakarta, Indonesia.
authors.forename: Theressa
authors.initials: T
authors.lastname: Subali
authors.affiliation: Department of Molecular Biology and Biotechnology, University of the Phillipines Los Banos, Laguna, Phillipines.
authors.forename: Fatima Carla T
authors.initials: FC
authors.lastname: Bertulfo
authors.affiliation: Virology and Cell Technology Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani, Thailand.
authors.forename: Phonphimon
authors.initials: P
authors.lastname: Wongthida
authors.affiliation: Virology and Cell Technology Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani, Thailand. Electronic address: anan.jon@biotec.or.th.
authors.forename: Anan
authors.initials: A
authors.lastname: Jongkaewwattana
mesh_terms: D000818:Animals; D000898:Antibiosis / Q000235:genetics; D060085:Coinfection; D004285:Dogs; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D009980:Influenza A virus / Q000235:genetics* / Q000378:metabolism; D009981:Influenza B virus / Q000235:genetics* / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D008958:Models, Molecular; D009154:Mutation; D009698:Nucleoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D012324:RNA-Dependent RNA Polymerase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014758:Viral Core Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
chemical_list: D009698:Nucleoproteins; D011994:Recombinant Proteins; D014758:Viral Core Proteins; D012324:RNA-Dependent RNA Polymerase
keywords: Influenza virus; Intertypic interference; Nucleoprotein