ArticleMedical microbiology and immunology2016
PA-X-associated early alleviation of the acute lung injury contributes to the attenuation of a highly pathogenic H5N1 avian influenza virus in mice.
Article in Medical microbiology and immunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 31 citations in OpenAlex.
- Long noncoding RNA#61 synergizes with viral PA-X to augment pyroptosis and attenuate the virulence of highly pathogenic H5N1 influenza virus in mice.Journal of virology · 2026Article
- The PA-X host shutoff site 100 V exerts a contrary effect on viral fitness of the highly pathogenic H7N9 influenza A virus in mice and chickens.Virulence · 2025Article
- PA and PA-X: two key proteins from segment 3 of the influenza viruses.Frontiers in cellular and infection microbiology · 2025Review
- Mechanisms and consequences of mRNA destabilization during viral infections.Virology journal · 2024Review
- The Role of Viral RNA Degrading Factors in Shutoff of Host Gene Expression.Annual review of virology · 2022Review
- Prediction of potential inhibitors against SARS-CoV-2 endoribonuclease: RNA immunity sensing.Journal of biomolecular structure & dynamics · 2022Article
- Identification of Amino Acid Residues Required for Inhibition of Host Gene Expression by Influenza Virus A/Viet Nam/1203/2004 H5N1 PA-X.Journal of virology · 2022Article
- Natural Selection of H5N1 Avian Influenza A Viruses with Increased PA-X and NS1 Shutoff Activity.Viruses · 2021Article
- Amino Acid Residues Involved in Inhibition of Host Gene Expression by Influenza A/Brevig Mission/1/1918 PA-X.Microorganisms · 2021Article
- Immunity to Influenza Infection in Humans.Cold Spring Harbor perspectives in medicine · 2021Review
- An outline of SARS-CoV-2 pathogenesis and the complement cascade of immune system.Bulletin of the National Research Centre · 2021Review
- Host Single Nucleotide Polymorphisms Modulating Influenza A Virus Disease in Humans.Pathogens (Basel, Switzerland) · 2019Review
- PA-X antagonises MAVS-dependent accumulation of early type I interferon messenger RNAs during influenza A virus infection.Scientific reports · 2019Article
- The Influenza A Virus Endoribonuclease PA-X Usurps Host mRNA Processing Machinery to Limit Host Gene Expression.Cell reports · 2019Article
- Mutation of Influenza A Virus PA-X Decreases Pathogenicity in Chicken Embryos and Can Increase the Yield of Reassortant Candidate Vaccine Viruses.Journal of virology · 2019Article
- Catalytic inactivation of influenza virus by iron oxide nanozyme.Theranostics · 2019Article
- Review
- PA-X: a key regulator of influenza A virus pathogenicity and host immune responses.Medical microbiology and immunology · 2018Review
- Functional Evolution of the 2009 Pandemic H1N1 Influenza Virus NS1 and PA in Humans.Journal of virology · 2018Article
- Host Shutoff in Influenza A Virus: Many Means to an End.Viruses · 2018Review
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PA-X is a novel discovered accessory protein encoded by the PA mRNA. Our previous study demonstrated that PA-X decreases the virulence of a highly pathogenic H5N1 strain A/Chicken/Jiangsu/k0402/2010 in mice. However, the underlying mechanism of virulence attenuation associated with PA-X is still unknown. In this study, we compared two PA-X-deficient mutant viruses and the parental virus in terms of induction of pathology and manipulation of host response in the mouse lung, stimulation of cell death and PA nuclear accumulation. We first found that down-regulated PA-X expression markedly aggravated the acute lung injury of the infected mice early on day 1 post-infection (p.i.). We then determined that loss of PA-X expression induced higher levels of cytokines, chemokines and complement-derived peptides (C3a and C5a) in the lung, especially at early time point's p.i. In addition, in vitro assays showed that the PA-X-deficient viruses enhanced cell death and increased expression of reactive oxygen species (ROS) in mammalian cells. Moreover, we also found that PA nuclear accumulation of the PA-X-null viruses accelerated in MDCK cells. These results demonstrate that PA-X decreases the level of complement components, ROS, cell death and inflammatory response, which may together contribute to the alleviated lung injury and the attenuation of the virulence of H5N1 virus in mice.
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