1887

Abstract

PB1-F2 is a pro-apoptotic polypeptide of many influenza A virus (FLUAV) isolates encoded by an alternative ORF of segment 2. A comprehensive GenBank search was conducted to analyse its prevalence. This search yielded 2226 entries of 80 FLUAV subtypes. Of these sequences, 87 % encode a PB1-F2 polypeptide greater than 78 aa. However, classic swine influenza viruses and human H1N1 isolates collected since 1950 harbour a truncated PB1-F2 sequence. While PB1-F2 of human H1N1 viruses terminates after 57 aa, classic swine H1N1 sequences have in-frame stop codons after 11, 25 and 34 codons. Of the avian sequences, 96 % encode a full-length PB1-F2. One genetic lineage of segment 2 sequences which is avian-like and different from the classic swine FLUAV comprises PB1-F2 sequences of porcine FLUAVs isolated in Europe (H1N1, H1N2, H3N2). Of these PB1-F2 sequences, 42 % also exhibit stop codons after 11, 25 and 34 codons. These amino acid positions are highly conserved among all FLUAV isolates irrespective of their origin. Molecular genetic analyses reveal that PB1-F2 is under constraint of the PB1 gene. The PB1-F2 polypeptide of FLUAVs isolated from European pigs is expressed in host cells as demonstrated by immunohistochemistry. Using different PB1-F2 versions fused to an enhanced GFP, mitochondrial localization is demonstrated for those PB1-F2 polypeptides which are greater than 78 aa while a truncated version (57 aa) shows a diffuse cytoplasmic distribution. This indicates similar properties and function of porcine and human FLUAV PB1-F2.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.82378-0
2007-02-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/88/2/536.html?itemId=/content/journal/jgv/10.1099/vir.0.82378-0&mimeType=html&fmt=ahah

References

  1. Brown I. H., Harris P. A., McCauley J. W., Alexander D. J. 1998; Multiple genetic reassortment of avian and human influenza A viruses in European pigs, resulting in the emergence of an H1N2 virus of novel genotype. J Gen Virol 79:2947–2955
    [Google Scholar]
  2. Castrucci M. R., Donatelli I., Sidoli L., Barigazzi G., Kawaoka Y., Webster R. G. 1993; Genetic reassortment between avian and human influenza A viruses in Italian pigs. Virology 193:503–506 [CrossRef]
    [Google Scholar]
  3. Castrucci M. R., Campitelli L., Ruggieri A., Barigazzi G., Sidoli L., Daniels R., Oxford J. S., Donatelli I. 1994; Antigenic and sequence analysis of H3 influenza virus haemagglutinins from pigs in Italy. J Gen Virol 75:371–379 [CrossRef]
    [Google Scholar]
  4. Chen W., Calvo P. A., Malide D., Gibbs J., Schubert U., Bacik I., Basta S., O'Neill R., Schickli J. other authors 2001; A novel influenza A virus mitochondrial protein that induces cell death. Nat Med 7:1306–1312 [CrossRef]
    [Google Scholar]
  5. Chen G. W., Yang C. C., Tsao K. C., Huang C. G., Lee L. A., Yang W. Z., Huang Y. L., Lin T. Y., Shih S. R. 2004; Influenza A virus PB1-F2 gene in recent Taiwanese isolates. Emerg Infect Dis 10:630–636 [CrossRef]
    [Google Scholar]
  6. Fu Y. X., Li W. H. 1993; Statistical tests of neutrality of mutations. Genetics 133:693–709
    [Google Scholar]
  7. Gibbs J. S., Malide D., Hornung F., Bennink J. R., Yewdell J. W. 2003; The influenza A virus PB1-F2 protein targets the inner mitochondrial membrane via a predicted basic amphipathic helix that disrupts mitochondrial function. J Virol 77:7214–7224 [CrossRef]
    [Google Scholar]
  8. Gregory V., Lim W., Cameron K., Bennett M., Klimov A., Hall H., Cox N., Hay A. J., Lin Y. 2001; Infection of a child in Hong Kong by an influenza A H3N2 virus closely related to viruses circulating in European pigs. J Gen Virol 82:1397–1406
    [Google Scholar]
  9. Guan Y., Shortridge K. F., Krauss S., Li P. H., Kawaoka Y., Webster R. G. 1996; Emergence of avian H1N1 influenza viruses in pigs in China. J Virol 70:8041–8046
    [Google Scholar]
  10. Karasin A. I., Carman S., Olsen C. W. 2006; Identification of human H1N2 and human–swine reassortant H1N2 and H1N1 influenza A viruses among pigs in Ontario. Canada: (2003 to 2005 J Clin Microbiol 44:1123–1126 [CrossRef]
    [Google Scholar]
  11. Kimura M. 1983 Neutral Theory of Molecular Evolution Cambridge, MA: Cambridge University Press;
    [Google Scholar]
  12. Krieg R. 2006; Entwicklung, Struktur-/Eigenschaftsoptimierung und Anwendung neuartiger multifunktioneller Chromogene und Fluorochrome für den histochemischen Nachweis von peroxidatischer Aktivität und die in vivo Markierung zellulärer Organellen. Eine transmissionsmikroskopische, fluoreszenzoptische und ein-/multiphotonenlasermikroskopische Untersuchung . Habilitationsschrift, Medizinische Fakultät der Friedrich-Schiller-Universität Jena, Germany
  13. Kumar S., Tamura K., Nei M. 2004; mega3: integrated software for Molecular Evolutionary Genetics Analysis and sequence alignment. Brief Bioinform 5:150–163 [CrossRef]
    [Google Scholar]
  14. Lamb R. A., Krug R. M. 1996; Orthomyxoviridae: the viruses and their replication. In Fields Virology , 3rd edn. pp  1353–1395 Edited by Fields B. N., Knipe D. M., Howley P. M. Philadelphia: Lippincott–Raven Publishers;
    [Google Scholar]
  15. Ludwig S., Pleschka S., Planz O., Wolff T. 2006; Ringing the alarm bells: signalling and apoptosis in influenza virus infected cells. Cell Microbiol 8:375–386 [CrossRef]
    [Google Scholar]
  16. Marozin S., Gregory V., Cameron K., Bennett M., Valette M., Aymard M., Foni E., Barigazzi G., Lin Y., Hay A. 2002; Antigenic and genetic diversity among swine influenza A H1N1 and H1N2 viruses in Europe. J Gen Virol 83:735–745
    [Google Scholar]
  17. McDonald J. H., Kreitman M. 1991; Adaptive protein evolution at the Adh locus in Drosophila . Nature 351:652–654 [CrossRef]
    [Google Scholar]
  18. Miyata T., Yasunaga T. 1980; Molecular evolution of mRNA: a method for estimating evolutionary rates of synonymous and amino acid substitutions from homologous nucleotide sequences and its application. J Mol Evol 16:23–36 [CrossRef]
    [Google Scholar]
  19. Nei M., Gojobori T. 1986; Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions. Mol Biol Evol 3:418–426
    [Google Scholar]
  20. Obenauer J. C., Denson J., Mehta P. K., Su X., Mukatira S., Finkelstein D. B., Xu X., Wang J., Ma J. other authors 2006; Large-scale sequence analysis of avian influenza isolates. Science 311:1576–1580 [CrossRef]
    [Google Scholar]
  21. Ross M. F., Kelso G. F., Blaikie F. H., James A. M., Cocheme H. M., Filipovska A., Da Ros T., Hurd T. R., Smith R. A., Murphy M. P. 2005; Lipophilic triphenylphosphonium cations as tools in mitochondrial bioenergetics and free radical biology. Biochemistry (Mosc) 70:222–230 [CrossRef]
    [Google Scholar]
  22. Rozas J., Sanches-DelBarrio J. C., Messeguer X., Rozas R. 2003; DnaSP, DNA polymorphism analyses by the coalescent and other methods. Bioinformatics 19:2496–2497 [CrossRef]
    [Google Scholar]
  23. Schmidtke M., Zell R., Bauer K., Krumbholz A., Schrader C., Suess J., Wutzler P. 2006; Amantadine resisitance among porcine H1N1, H1N2, and H3N2 influenza A viruses isolated in Germany between 1981 and 2001. Intervirology 49:286–293 [CrossRef]
    [Google Scholar]
  24. Schrader C., Süss J. 2003; Genetic characterization of a porcine H1N2 influenza virus strain isolated in Germany. Intervirology 46:66–70 [CrossRef]
    [Google Scholar]
  25. Schrader C., Süss J. 2004; Molecular epidemiology of porcine H3N2 influenza A viruses isolated in Germany between 1982 and 2001. Intervirology 47:72–77 [CrossRef]
    [Google Scholar]
  26. Tajima F. 1989; Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics 123:585–595
    [Google Scholar]
  27. Yamada H., Chounan R., Higashi Y., Kurihara N., Kido H. 2004; Mitochondrial targeting sequence of the influenza A virus PB1-F2 protein and its function in mitochondria. FEBS Lett 578:331–336 [CrossRef]
    [Google Scholar]
  28. Yang Z. 1997; paml: a program package for phylogenetic analysis by maximum likelihood. Comput Appl Biosci 13:555–556
    [Google Scholar]
  29. Zamarin D., Garcia-Sastre A., Xiao X., Wang R., Palese P. 2005; Influenza virus PB1-F2 protein induces cell death through mitochondrial ANT3 and VDAC1. PLoS Pathog 1: doi [View Article]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.82378-0
Loading
/content/journal/jgv/10.1099/vir.0.82378-0
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF

Supplementary material 2

PDF
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