ArticlePLoS pathogens2016
Selective Degradation of Host RNA Polymerase II Transcripts by Influenza A Virus PA-X Host Shutoff Protein.
Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
94 citing papers in PubMed, 2 syntheses or guidelines pooled it, 141 citations in OpenAlex.
- Neutrophil Extracellular Traps in Viral Infections.Pathogens (Basel, Switzerland) · 2025Pooled it
- Pooled it
- Evolution of a truncated nucleocapsid protein enhances SARS-CoV-2 fitness by suppressing antiviral responses.PLoS biology · 2026Article
- CircRNA expression profiling in H1N1-infected primary human tracheobronchial epithelial cells identifies candidate immune-related circRNAs validated in A549 cells.Archives of virology · 2026Article
- N-terminal acetylation controls multiple functional aspects of the influenza A virus ribonuclease PA-X.Journal of virology · 2026Article
- Article
- Impaired host shutoff is a fitness cost associated with baloxavir marboxil resistance mutations in influenza A virus PA/PA-X nuclease domain.PLoS pathogens · 2026Article
- Dual roles for influenza A protein PA-X: limiting inflammatory response and disrupting MHC I antigen presentation in human respiratory epithelium.bioRxiv : the preprint server for biology · 2026Article
- The ribosomal landscape in influenza A virus infection: from molecular mechanisms to clinical relevance.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- 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
- T Cell Responses to Influenza Infections in Cattle.Viruses · 2025Review
- N-terminal acetylation controls multiple functional aspects of the influenza A virus ribonuclease PA-X.bioRxiv : the preprint server for biology · 2025Article
- Nuclear warfare: pathogen manipulation of the nuclear pore complex and nuclear functions.mBio · 2025Review
- Coronavirus endoribonuclease nsp15 suppresses host protein synthesis and evades PKR-eIF2α-mediated translation shutoff to ensure viral protein synthesis.PLoS pathogens · 2025Article
- Emerging threats of H5N1 clade 2.3.4.4b: cross-species transmission, pathogenesis, and pandemic risk.Frontiers in cellular and infection microbiology · 2025Review
- Influenza A virus NS1 effector domain is required for PA-X-mediated host shutoff in infected cells.Journal of virology · 2024Article
- Synthetic Cell Lines for Inducible Packaging of Influenza A Virus.ACS synthetic biology · 2024Article
- Mechanisms and consequences of mRNA destabilization during viral infections.Virology journal · 2024Review
- Influenza A virus inhibits TET2 expression by endoribonuclease PA-X to attenuate type I interferon signaling and promote viral replication.PLoS pathogens · 2023Article
- Cut site preference allows influenza A virus PA-X to discriminate between host and viral mRNAs.Nature microbiology · 2023Article
34 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Influenza A viruses (IAVs) inhibit host gene expression by a process known as host shutoff. Host shutoff limits host innate immune responses and may also redirect the translation apparatus to the production of viral proteins. Multiple IAV proteins regulate host shutoff, including PA-X, a ribonuclease that remains incompletely characterized. We report that PA-X selectively targets host RNA polymerase II (Pol II) transcribed mRNAs, while sparing products of Pol I and Pol III. Interestingly, we show that PA-X can also target Pol II-transcribed RNAs in the nucleus, including non-coding RNAs that are not destined to be translated, and reporter transcripts with RNA hairpin structures that block ribosome loading. Transcript degradation likely occurs in the nucleus, as PA-X is enriched in the nucleus and its nuclear localization correlates with reduction in target RNA levels. Complete degradation of host mRNAs following PA-X-mediated endonucleolytic cleavage is dependent on the host 5'->3'-exonuclease Xrn1. IAV mRNAs are structurally similar to host mRNAs, but are synthesized and modified at the 3' end by the action of the viral RNA-dependent RNA polymerase complex. Infection of cells with wild-type IAV or a recombinant PA-X-deficient virus revealed that IAV mRNAs resist PA-X-mediated degradation during infection. At the same time, loss of PA-X resulted in changes in the synthesis of select viral mRNAs and a decrease in viral protein accumulation. Collectively, these results significantly advance our understanding of IAV host shutoff, and suggest that the PA-X causes selective degradation of host mRNAs by discriminating some aspect of Pol II-dependent RNA biogenesis in the nucleus.
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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.