1887

Abstract

For influenza A and B viruses to be infectious, they require eight viral RNA (vRNA) genome segments to be packaged into virions. For efficient packaging, influenza A viruses utilize -acting vRNA sequences, containing both non-coding and protein coding regions of each segment. Whether influenza B viruses have similar packaging signals is unknown. Here we show that coding regions at the 3′ and 5′ ends of the influenza B virus vRNA segment 4 are required for genome packaging, with the first 30 nt at each end essential for this process. Synonymous mutation of these regions led to virus attenuation, an increase in defective particle production and a reduction in packaging of multiple vRNAs. Overall, our data suggest that the influenza B virus vRNA gene segments likely interact with each other during the packaging process, which is driven by -acting packaging signals that extend into protein coding regions of the vRNA.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.000358
2016-02-01
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/97/2/306.html?itemId=/content/journal/jgv/10.1099/jgv.0.000358&mimeType=html&fmt=ahah

References

  1. Barclay W. S., Palese P. 1995; Influenza B viruses with site-specific mutations introduced into the HA gene. J Virol 69:1275–1279[PubMed]
    [Google Scholar]
  2. Chou Y. Y., Heaton N. S., Gao Q., Palese P., Singer R. H., Lionnet T. 2013; Colocalization of different influenza viral RNA segments in the cytoplasm before viral budding as shown by single-molecule sensitivity FISH analysis. PLoS Pathog 9:e1003358 [View Article][PubMed]
    [Google Scholar]
  3. Donald H. B., Isaacs A. 1954; Counts of influenza virus particles. J Gen Microbiol 10:457–464 [View Article][PubMed]
    [Google Scholar]
  4. Duhaut S. D., Dimmock N. J. 1998; Heterologous protection of mice from a lethal human H1N1 influenza A virus infection by H3N8 equine defective interfering virus: comparison of defective RNA sequences isolated from the DI inoculum and mouse lung. Virology 248:241–253 [View Article][PubMed]
    [Google Scholar]
  5. Duhaut S., Dimmock N. J. 2000; Approximately 150 nucleotides from the 5′ end of an influenza A segment 1 defective virion RNA are needed for genome stability during passage of defective virus in infected cells. Virology 275:278–285 [View Article][PubMed]
    [Google Scholar]
  6. Duhaut S. D., McCauley J. W. 1996; Defective RNAs inhibit the assembly of influenza virus genome segments in a segment-specific manner. Virology 216:326–337 [View Article][PubMed]
    [Google Scholar]
  7. Essere B., Yver M., Gavazzi C., Terrier O., Isel C., Fournier E., Giroux F., Textoris J., Julien T., other authors. 2013; Critical role of segment-specific packaging signals in genetic reassortment of influenza A viruses. Proc Natl Acad Sci U S A 110:E3840–E3848 [View Article][PubMed]
    [Google Scholar]
  8. Fournier E., Moules V., Essere B., Paillart J. C., Sirbat J. D., Isel C., Cavalier A., Rolland J. P., Thomas D., other authors. 2012; A supramolecular assembly formed by influenza A virus genomic RNA segments. Nucleic Acids Res 40:2197–2209 [View Article][PubMed]
    [Google Scholar]
  9. Fujii Y., Goto H., Watanabe T., Yoshida T., Kawaoka Y. 2003; Selective incorporation of influenza virus RNA segments into virions. Proc Natl Acad Sci U S A 100:2002–2007 [View Article][PubMed]
    [Google Scholar]
  10. Fujii K., Fujii Y., Noda T., Muramoto Y., Watanabe T., Takada A., Goto H., Horimoto T., Kawaoka Y. 2005; Importance of both the coding and the segment-specific noncoding regions of the influenza A virus NS segment for its efficient incorporation into virions. J Virol 79:3766–3774 [View Article][PubMed]
    [Google Scholar]
  11. Gavazzi C., Yver M., Isel C., Smyth R. P., Rosa-Calatrava M., Lina B., Moulès V., Marquet R. 2013; A functional sequence-specific interaction between influenza A virus genomic RNA segments. Proc Natl Acad Sci U S A 110:16604–16609 [View Article][PubMed]
    [Google Scholar]
  12. Gerber M., Isel C., Moules V., Marquet R. 2014; Selective packaging of the influenza A genome and consequences for genetic reassortment. Trends Microbiol 22:446–455 [View Article][PubMed]
    [Google Scholar]
  13. Gog J. R., Afonso E. S., Dalton R. M., Leclercq I., Tiley L., Elton D., von Kirchbach J. C., Naffakh N., Escriou N., Digard P. 2007; Codon conservation in the influenza A virus genome defines RNA packaging signals. Nucleic Acids Res 35:1897–1907 [View Article][PubMed]
    [Google Scholar]
  14. Goto H., Muramoto Y., Noda T., Kawaoka Y. 2013; The genome-packaging signal of the influenza A virus genome comprises a genome incorporation signal and a genome-bundling signal. J Virol 87:11316–11322 [View Article][PubMed]
    [Google Scholar]
  15. Hoffmann E., Mahmood K., Yang C. F., Webster R. G., Greenberg H. B., Kemble G. 2002; Rescue of influenza B virus from eight plasmids. Proc Natl Acad Sci U S A 99:11411–11416 [View Article][PubMed]
    [Google Scholar]
  16. Hutchinson E. C., von Kirchbach J. C., Gog J. R., Digard P. 2010; Genome packaging in influenza A virus. J Gen Virol 91:313–328 [View Article][PubMed]
    [Google Scholar]
  17. Katz G., Benkarroum Y., Wei H., Rice W. J., Bucher D., Alimova A., Katz A., Klukowska J., Herman G. T., Gottlieb P. 2014; Morphology of influenza B/Lee/40 determined by cryo-electron microscopy. PLoS One 9:e88288 [View Article][PubMed]
    [Google Scholar]
  18. Lakdawala S. S., Wu Y., Wawrzusin P., Kabat J., Broadbent A. J., Lamirande E. W., Fodor E., Altan-Bonnet N., Shroff H., Subbarao K. 2014; Influenza A virus assembly intermediates fuse in the cytoplasm. PLoS Pathog 10:e1003971 [View Article][PubMed]
    [Google Scholar]
  19. Luytjes W., Krystal M., Enami M., Parvin J. D., Palese P. 1989; Amplification, expression, and packaging of foreign gene by influenza virus. Cell 59:1107–1113 [View Article][PubMed]
    [Google Scholar]
  20. Marsh G. A., Hatami R., Palese P. 2007; Specific residues of the influenza A virus hemagglutinin viral RNA are important for efficient packaging into budding virions. J Virol 81:9727–9736 [View Article][PubMed]
    [Google Scholar]
  21. Nayak D. P., Sivasubramanian N., Davis A. R., Cortini R., Sung J. 1982; Complete sequence analyses show that two defective interfering influenza viral RNAs contain a single internal deletion of a polymerase gene. Proc Natl Acad Sci U S A 79:2216–2220 [View Article][PubMed]
    [Google Scholar]
  22. Noda T., Sagara H., Yen A., Takada A., Kida H., Cheng R. H., Kawaoka Y. 2006; Architecture of ribonucleoprotein complexes in influenza A virus particles. Nature 439:490–492 [View Article][PubMed]
    [Google Scholar]
  23. Palese P., Shaw M. L. 2007; Orthomyxoviridae: the viruses and their replication. In Fields Virology, 5th edn. pp 1647–1689Edited by Knipe D. M., Howley P. M. Philadelphia: Lippincott Williams and Wilkins;
    [Google Scholar]
  24. Sherry L., Smith M., Davidson S., Jackson D. 2014; The N terminus of the influenza B virus nucleoprotein is essential for virus viability, nuclear localization, and optimal transcription and replication of the viral genome. J Virol 88:12326–12338 [View Article][PubMed]
    [Google Scholar]
  25. Watanabe T., Watanabe S., Noda T., Fujii Y., Kawaoka Y. 2003; Exploitation of nucleic acid packaging signals to generate a novel influenza virus-based vector stably expressing two foreign genes. J Virol 77:10575–10583 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.000358
Loading
/content/journal/jgv/10.1099/jgv.0.000358
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error