tetano
Editor, Senior Moderator
J Infect Dis. 2013 Aug 27. [Epub ahead of print]
New virulence determinants contribute to the enhanced immune response and reduced virulence of an influenza A virus A/PR8/34 variant.
Liedmann S, Hrincius ER, Anhlan D, McCullers JA, Ludwig S, Ehrhardt C.
Source
Institute of Molecular Virology (IMV), Center for Molecular Biology of Inflammation (ZMBE), University of Muenster, Von Esmarch-Str. 56, D-48149 Muenster, Germany.
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. In the current study we phenotypically and genotypically compared two 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 NP 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.
PMID:
23983213
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23983213
New virulence determinants contribute to the enhanced immune response and reduced virulence of an influenza A virus A/PR8/34 variant.
Liedmann S, Hrincius ER, Anhlan D, McCullers JA, Ludwig S, Ehrhardt C.
Source
Institute of Molecular Virology (IMV), Center for Molecular Biology of Inflammation (ZMBE), University of Muenster, Von Esmarch-Str. 56, D-48149 Muenster, Germany.
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. In the current study we phenotypically and genotypically compared two 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 NP 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.
PMID:
23983213
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23983213