title: Single nucleoprotein residue determines influenza A virus sensitivity to an intertypic suppression mechanism.
abstract: Several mechanisms underlying intertypic interference between co-infecting influenza types A and B viruses (IAV and IBV) have been proposed. We have recently described one in which IBV's nucleoprotein (BNP) sequestered IAV's nucleoprotein (ANP) and suppressed IAV polymerase and growth. However, its anti-IAV capacity and limitations have not been fully explored. Here, we showed that BNP's inhibitory effect was more potent toward a wide array of avian IAVs, whereas human IAVs revealed moderate resistance. BNP sensitivity was largely determined by ANP's residue 343 at the NP oligomerization interface. An avian IAV polymerase carrying an NP-V343L mutation switched from being highly BNP-sensitive to moderately BNP-resistant, and vice versa for a human IAV polymerase carrying a reverse mutation. To highlight its capacity, we demonstrated that the polymerases of highly-pathogenic H5N1 and the pandemic 2009 (H1N1) strains are strongly inhibited by BNP. Our work provides insights into lineage-specific sensitivity to BNP-mediated intertypic interference.
authors.affiliation: Virology and Cell Technology Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathum Thani 12120, 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), Pathum Thani 12120, Thailand.
authors.forename: Samaporn
authors.initials: S
authors.lastname: Teeravechyan
authors.affiliation: Center for Research and Innovation, Faculty of Medical Technology, Mahidol University, 999 Phutthamonthon 4 Road, Salaya, Nakhon Pathom 73170, Thailand.
authors.forename: Pilaipan
authors.initials: P
authors.lastname: Puthavathana
authors.affiliation: Virology and Cell Technology Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathum Thani 12120, Thailand.
authors.forename: Anan
authors.initials: A
authors.lastname: Jongkaewwattana
authors.affiliation: Virology and Cell Technology Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathum Thani 12120, Thailand. Electronic address: peera.jar@biotec.or.th.
authors.forename: Peera
authors.initials: P
authors.lastname: Jaru-Ampornpan
mesh_terms: D000818:Animals; D001717:Birds; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000502:physiology; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics / Q000502:physiology; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000502:physiology; D009980:Influenza A virus / Q000235:genetics*; D009981:Influenza B virus / Q000235:genetics* / Q000502:physiology; D005585:Influenza in Birds / Q000523:psychology* / Q000821:virology*; D007251:Influenza, Human / Q000821:virology*; D009154:Mutation; D009698:Nucleoproteins / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide
chemical_list: D009698:Nucleoproteins
keywords: Avian influenza virus; Influenza virus; Intertypic interference; Nucleoprotein