ArticleJournal of virology2020
An R195K Mutation in the PA-X Protein Increases the Virulence and Transmission of Influenza A Virus in Mammalian Hosts.
Article in Journal of virology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 39 citations in OpenAlex.
- Emerged N193S mutation of PA-X protein disabled the immunity of mucosal dendritic cells for regulating virulence of clade 2.3.4.4b H5 subtype virus.Emerging microbes & infections · 2026Article
- Molecular characterization and pathogenicity of H9N2 avian influenza viruses in poultry in Shandong Province, China, 2021-2023.Poultry science · 2026Article
- Article
- 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
- Phylogenetic and Molecular Characteristics of An H3N8 Avian Influenza Virus Detected in Wild Birds - Beijing, China, September 2024.China CDC weekly · 2025Article
- Chronic Diseases and Influenza Vaccines.Vaccines · 2025Review
- Landscape of H5 Infections in ASEAN Region: Past Insights, Present Realities, & Future Strategies.Viruses · 2025Review
- PA and PA-X: two key proteins from segment 3 of the influenza viruses.Frontiers in cellular and infection microbiology · 2025Review
- Novel mutation N588 residue in the NS1 protein of feline parvovirus greatly augments viral replication.Journal of virology · 2024Article
- Article
- Detection and Characterization of an H9N2 Influenza A Virus in the Egyptian Rousette Bat in Limpopo, South Africa.Viruses · 2023Article
- Article
- Key amino acid position 272 in neuraminidase determines the replication and virulence of H5N6 avian influenza virus in mammals.iScience · 2022Article
- Article
- 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
- Emergence and Evolution of Novel Canine-Avian Reassortant H3N2 Influenza A Viruses in Duck in Leizhou Peninsula, China.Frontiers in microbiology · 2022Article
- Reassortant Highly Pathogenic H5N6 Avian Influenza Virus Containing Low Pathogenic Viral Genes in a Local Live Poultry Market, Vietnam.Current microbiology · 2021Article
- The N-terminal domain of SARS-CoV-2 nsp1 plays key roles in suppression of cellular gene expression and preservation of viral gene expression.Cell reports · 2021Article
- Natural Selection of H5N1 Avian Influenza A Viruses with Increased PA-X and NS1 Shutoff Activity.Viruses · 2021Article
- Innate Antiviral Cytokine Response to Swine Influenza Virus by Swine Respiratory Epithelial Cells.Journal of virology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
In the 21st century, the emergence of H7N9 and H1N1/2009 influenza viruses, originating from animals and causing severe human infections, has prompted investigations into the genetic alterations required for cross-species transmission. We previously found that replacement of the human-origin PA gene segment in avian influenza virus (AIV) could overcome barriers to cross-species transmission. Recently, it was reported that the PA gene segment encodes both the PA protein and a second protein, PA-X. Here, we investigated the role of PA-X. We found that an H9N2 avian influenza reassortant virus bearing a human-origin H1N1/2009 PA gene was attenuated in mice after the loss of PA-X. Reverse genetics analyses of PA-X substitutions conserved in human influenza viruses indicated that R195K, K206R, and P210L substitutions conferred significantly increased replication and pathogenicity on H9N2 virus in mice and ferrets. PA-X R195K was present in all human H7N9 and H1N1/2009 viruses and predominated in human H5N6 viruses. Compared with PA-X 195R, H7N9 influenza viruses bearing PA-X 195K showed increased replication and transmission in ferrets. We further showed that PA-X 195K enhanced lung inflammatory responses, potentially due to decreased host shutoff function. A competitive transmission study in ferrets indicated that 195K provides a replicative advantage over 195R in H1N1/2009 viruses. In contrast, PA-X 195K did not influence the virulence of H9N2 AIV in chickens, suggesting that the effects of the substitution were mammal specific. Therefore, future surveillance efforts should scrutinize this region of PA-X because of its potential impact on cross-species transmission of influenza viruses.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.