New virulence determinants contribute to the enhanced immune response and reduced virulence of an influenza a virus A/PR8/34 variant

Swantje Liedmann, Eike R. Hrincius, Darisuren Anhlan, Jonathan Mccullers, Stephan Ludwig, Christina Ehrhardt

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The identification of amino acid motifs responsible for increased virulence and/or transmission of influenza viruses is of enormous importance to predict pathogenicity of upcoming influenza strains. We phenotypically and genotypically compared 2 variants of influenza virus A/PR/8/34 with different passage histories. The analysis revealed differences in virulence due to an altered type I interferon (IFN) induction, as evidenced by experiments using IFNAR -/- mice. Interestingly, these differences were not due to altered functions of the well-known viral IFN antagonists NS1 or PB1-F2. Using reassortant viruses, we showed that differences in the polymerase proteins and nucleoprotein determined the altered virulence. In particular, changes in PB1 and PA contributed to an altered host type I IFN response, indicating IFN antagonistic properties of these proteins. Thus, PB1 and PA appear to harbor previously unknown virulence markers, which may prove helpful in assessing the risk potential of emerging influenza viruses.

Original languageEnglish (US)
Pages (from-to)532-541
Number of pages10
JournalJournal of Infectious Diseases
Volume209
Issue number4
DOIs
StatePublished - Feb 15 2014

Fingerprint

Influenza A virus
Virulence
Interferon Type I
Orthomyxoviridae
Interferons
Reassortant Viruses
Amino Acid Motifs
Nucleoproteins
Human Influenza
Proteins

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Infectious Diseases

Cite this

New virulence determinants contribute to the enhanced immune response and reduced virulence of an influenza a virus A/PR8/34 variant. / Liedmann, Swantje; Hrincius, Eike R.; Anhlan, Darisuren; Mccullers, Jonathan; Ludwig, Stephan; Ehrhardt, Christina.

In: Journal of Infectious Diseases, Vol. 209, No. 4, 15.02.2014, p. 532-541.

Research output: Contribution to journalArticle

Liedmann, Swantje ; Hrincius, Eike R. ; Anhlan, Darisuren ; Mccullers, Jonathan ; Ludwig, Stephan ; Ehrhardt, Christina. / New virulence determinants contribute to the enhanced immune response and reduced virulence of an influenza a virus A/PR8/34 variant. In: Journal of Infectious Diseases. 2014 ; Vol. 209, No. 4. pp. 532-541.
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