Limited compatibility between the RNA polymerase components of influenza virus type A and B

Iwatsuki‐Horimoto, Kiyoko; Hatta, Yasuko; Hatta, Masato; Muramoto, Yukiko; Chen, Hualan; Kawaoka, Yoshihiro; Horimoto, Taisuke

doi:10.1016/j.virusres.2008.03.010

Cited by 17 publications

(15 citation statements)

References 28 publications

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“…Although recombinant chimeric influenza A/B viruses have been created, suggesting that portions of influenza B virus glycoproteins can replace the function of influenza A virus glycoproteins, substantial genetic modifications of the polypeptides were required for their successful rescue (17)(18)(19). Additionally, the RNA-dependent RNA polymerase (RdRp) of influenza A or B virus has been shown to transcribe genes flanked by the heterotypic promoter sequences (20)(21)(22) found in the terminal noncoding regions (NCRs) of each vRNA (23,24). Influenza A virus vRNA can direct the incorporation of specific segments into budding virions, so that each nascent infectious virus contains a set of eight unique vRNA molecules (reviewed in reference 25).…”

mentioning

confidence: 99%

Influenza A and B Virus Intertypic Reassortment through Compatible Viral Packaging Signals

Baker

Nogales

Finch

et al. 2014

J Virol

104

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Influenza A and B viruses cocirculate in humans and together cause disease and seasonal epidemics. These two types of influenza viruses are evolutionarily divergent, and exchange of genetic segments inside coinfected cells occurs frequently within types but never between influenza A and B viruses. Possible mechanisms inhibiting the intertypic reassortment of genetic segments could be due to incompatible protein functions of segment homologs, a lack of processing of heterotypic segments by influenza virus RNA-dependent RNA polymerase, an inhibitory effect of viral proteins on heterotypic virus function, or an inability to specifically incorporate heterotypic segments into budding virions. Here, we demonstrate that the full-length hemagglutinin (HA) of prototype influenza B viruses can complement the function of multiple influenza A viruses. We show that viral noncoding regions were sufficient to drive gene expression for either type A or B influenza virus with its cognate or heterotypic polymerase. The native influenza B virus HA segment could not be incorporated into influenza A virus virions. However, by adding the influenza A virus packaging signals to full-length influenza B virus glycoproteins, we rescued influenza A viruses that possessed HA, NA, or both HA and NA of influenza B virus. Furthermore, we show that, similar to single-cycle infectious influenza A virus, influenza B virus cannot incorporate heterotypic transgenes due to packaging signal incompatibilities. Altogether, these results demonstrate that the lack of influenza A and B virus reassortants can be attributed at least in part to incompatibilities in the virus-specific packaging signals required for effective segment incorporation into nascent virions. IMPORTANCEReassortment of influenza A or B viruses provides an evolutionary strategy leading to unique genotypes, which can spawn influenza A viruses with pandemic potential. However, the mechanism preventing intertypic reassortment or gene exchange between influenza A and B viruses is not well understood. Nucleotides comprising the coding termini of each influenza A virus gene segment are required for specific segment incorporation during budding. Whether influenza B virus shares a similar selective packaging strategy or if packaging signals prevent intertypic reassortment remains unknown. Here, we provide evidence suggesting a similar mechanism of influenza B virus genome packaging. Furthermore, by appending influenza A virus packaging signals onto influenza B virus segments, we rescued recombinant influenza A/B viruses that could reassort in vitro with another influenza A virus. These findings suggest that the divergent evolution of packaging signals aids with the speciation of influenza A and B viruses and is in part responsible for the lack of intertypic viral reassortment.

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mentioning

confidence: 99%

Influenza A and B Virus Intertypic Reassortment through Compatible Viral Packaging Signals

Baker

Nogales

Finch

et al. 2014

J Virol

104

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“…In a recent report, it was shown that activity for the type B polymerase machin-ery with a type A promoter depends on the specific RNA segment and that the levels of activity differ between type B strains. 33 Using plasmid transfection they observed that type B polymerase machinery that is composed of homologous subunits is functional with a type A promoter albeit to a variable extent depending upon the segments from which the regions downstream of the promoter sequence were derived. These authors did not assess delivery of the polymerase genes by virus infection which may explain the greater specificity we observed.…”

Section: Discussionmentioning

confidence: 99%

“…There was some level of cross‐induction between influenza A and B viruses, but the induction by the homologous virus was many‐fold higher than by the heterologous virus. In a recent report, it was shown that activity for the type B polymerase machinery with a type A promoter depends on the specific RNA segment and that the levels of activity differ between type B strains 33 . Using plasmid transfection they observed that type B polymerase machinery that is composed of homologous subunits is functional with a type A promoter albeit to a variable extent depending upon the segments from which the regions downstream of the promoter sequence were derived.…”

Section: Discussionmentioning

confidence: 99%

Influenza virus assays based on virus‐inducible reporter cell lines

Li¹,

Larrimer²,

Curtiss³

et al. 2009

Influenza Resp Viruses

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Background Virus‐inducible reporter genes have been used as the basis of virus detection and quantitation assays for a number of viruses. A strategy for influenza A virus‐induction of a reporter gene was recently described. In this report, we describe the extension of this strategy to influenza B virus, the generation of stable cell lines with influenza A and B virus‐inducible reporter genes, and the use of these cells in various clinically relevant viral assays. Each of the cell lines described herein constitutively express an RNA transcript that contains a reporter gene coding region flanked by viral 5′‐ and 3′‐untranslated regions (UTR) and therefore mimics an influenza virus genomic segment. Upon infection of the cells with influenza virus the virus‐inducible reporter gene segment (VIRGS) is replicated and transcribed by the viral polymerase complex resulting in reporter gene expression. Findings Reporter gene induction occurs after infection with a number of laboratory strains and clinical isolates of influenza virus including several H5N1 strains. The induction is dose‐dependent and highly specific for influenza A or influenza B viruses. Conclusions These cell lines provide the basis of simple, rapid, and objective assays that involve virus quantitation such as determination of viral titer, assessment of antiviral susceptibility, and determination of antibody neutralization titer. These cell lines could be very useful for influenza virus researchers and vaccine manufacturers.

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“…Several studies have used plasmid transfection to reconstitute polymerases in cells to assess the compatibility of influenza types A and B polymerase components and type-specific polymerase complexes with viral-like RNAs containing promoters derived from influenza A or B virus gene segments. Overall homologous combinations show the best activity and although the incompatibility is not absolute, it most likely contributes to the inability of viruses of different types to reassort (Crescenzo-Chaigne et al, 1999;Iwatsuki-Horimoto et al, 2008).…”

Section: Influenza B Virus Rna Non-coding Sequencesmentioning

confidence: 99%