An Overlapping Protein-Coding Region in Influenza A Virus Segment 3 Modulates the Host Response
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- 13 July 2012
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 337 (6091) , 199-204
- https://doi.org/10.1126/science.1222213
Abstract
Influenza A virus (IAV) infection leads to variable and imperfectly understood pathogenicity. We report that segment 3 of the virus contains a second open reading frame (“X-ORF”), accessed via ribosomal frameshifting. The frameshift product, termed PA-X, comprises the endonuclease domain of the viral PA protein with a C-terminal domain encoded by the X-ORF and functions to repress cellular gene expression. PA-X also modulates IAV virulence in a mouse infection model, acting to decrease pathogenicity. Loss of PA-X expression leads to changes in the kinetics of the global host response, which notably includes increases in inflammatory, apoptotic, and T lymphocyte–signaling pathways. Thus, we have identified a previously unknown IAV protein that modulates the host response to infection, a finding with important implications for understanding IAV pathogenesis.This publication has 36 references indexed in Scilit:
- Suppression of cytokine storm with a sphingosine analog provides protection against pathogenic influenza virusProceedings of the National Academy of Sciences, 2011
- Stimulation of stop codon readthrough: frequent presence of an extended 3′ RNA structural elementNucleic Acids Research, 2011
- Immunity to seasonal and pandemic influenza A virusesMicrobes and Infection, 2011
- Immunization with 1976 swine H1N1- or 2009 pandemic H1N1-inactivated vaccines protects mice from a lethal 1918 influenza infectionInfluenza and Other Respiratory Viruses, 2011
- Influenza Virus Evolution, Host Adaptation, and Pandemic FormationPublished by Elsevier ,2010
- Mechanisms and functional implications of the degradation of host RNA polymerase II in influenza virus infected cellsVirology, 2010
- Identification of the domains of the influenza A virus M1 matrix protein required for NP binding, oligomerization and incorporation into virionsJournal of General Virology, 2007
- Codon conservation in the influenza A virus genome defines RNA packaging signalsNucleic Acids Research, 2007
- Genomic analysis of increased host immune and cell death responses induced by 1918 influenza virusNature, 2006
- Basic Local Alignment Search ToolJournal of Molecular Biology, 1990