PA-X antagonises MAVS-dependent accumulation of early type I interferon messenger RNAs during influenza A virus infection

• Published in: Scientific reports 2019-05, Vol.9 (1), p.7216-7216, Article 7216
• Main Authors: Rigby, Rachel E., Wise, Helen M., Smith, Nikki, Digard, Paul, Rehwinkel, Jan
• Format: Article
• Language: English
• Subjects: 38/39; 631/250/262/2106/2518; 631/326/596/1578; 64/60; 96/95; Adaptor Proteins, Signal Transducing - deficiency; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Animals; Humanities and Social Sciences; Immune response; Immune system; Immunity, Innate; Infections; Influenza; Influenza A; Influenza A virus - metabolism; Influenza A virus - physiology; Innate immunity; Interferon; Interferon Type I - genetics; Interferon Type I - metabolism; Lung - metabolism; Lung - virology; Membrane Glycoproteins - deficiency; Membrane Glycoproteins - genetics; Mice; Mice, Inbred C57BL; Mice, Knockout; multidisciplinary; Nucleic acids; Orthomyxoviridae Infections - pathology; Orthomyxoviridae Infections - virology; Repressor Proteins - deficiency; Repressor Proteins - genetics; Repressor Proteins - metabolism; RNA, Messenger - metabolism; Science; Science (multidisciplinary); Signal Transduction; Toll-Like Receptor 7 - deficiency; Toll-Like Receptor 7 - genetics; Viral infections; Viral Nonstructural Proteins - deficiency; Viral Nonstructural Proteins - genetics; Viral Nonstructural Proteins - metabolism; Viruses
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-43632-6

The sensing of viral nucleic acids by the innate immune system activates a potent antiviral response in the infected cell, a key component of which is the expression of genes encoding type I interferons (IFNs). Many viruses counteract this response by blocking the activation of host nucleic acid sensors. The evolutionarily conserved influenza A virus (IAV) protein PA-X has been implicated in suppressing the host response to infection, including the expression of type I IFNs. Here, we characterise this further using a PA-X-deficient virus of the mouse-adapted PR8 strain to study activation of the innate immune response in a mouse model of the early response to viral infection. We show that levels of Ifna4 and Ifnb1 mRNAs in the lungs of infected mice were elevated in the absence of PA-X and that this was completely dependent on MAVS. This therefore suggests a role for PA-X in preventing the accumulation of early type I IFN mRNAs in the lung during IAV infection.