ArticlePLoS pathogens2022
p21 restricts influenza A virus by perturbing the viral polymerase complex and upregulating type I interferon signaling.
Article in PLoS pathogens, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
- Senolytic Treatment Reduces Acute and Chronic Lung Inflammation in an Aged Mouse Model of Influenza.Aging cell · 2026Article
- Poly(ADP-ribose) glycohydrolase enforces p21 degradation via dePARylation to promote gastric cancer progression.The Journal of clinical investigation · 2026Article
- Efficient airborne transmission of influenza D virus in ferret models and serological evidence of human exposure in Northeast China.Emerging microbes & infections · 2025Article
- Network pharmacology-based study to investigate the mechanism of compound houttuynia mixture against influenza virus infection by suppressing TLR7/MyD88 signaling pathway.Journal of traditional and complementary medicine · 2025Article
- Restriction of influenza A virus replication by host DCAF7-CRL4B axis.Journal of virology · 2025Article
- Impact of inactivated vaccine on transmission and evolution of H9N2 avian influenza virus in chickens.NPJ vaccines · 2025Article
- A Susceptible Cell-Selective Delivery (SCSD) of mRNA-Encoded Cas13d Against Influenza Infection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- CRTC3 restricts SARS-CoV-2 replication and is antagonized by CREB.Virologica Sinica · 2025Article
- Influenza Virus Host Restriction Factors: The ISGs and Non-ISGs.Pathogens (Basel, Switzerland) · 2024Review
- Immune response in influenza virus infection and modulation of immune injury by viral neuraminidase.Virology journal · 2023Review
- Host DNA Demethylation Induced by DNMT1 Inhibition Up-Regulates Antiviral OASL Protein during Influenza a Virus Infection.Viruses · 2023Article
- Coptisine Inhibits Influenza Virus Replication by Upregulating p21.Molecules (Basel, Switzerland) · 2023Article
- NOG1 downregulates type I interferon production by targeting phosphorylated interferon regulatory factor 3.PLoS pathogens · 2023Article
- The synergistic effect of residues 32T and 550L in the PA protein of H5 subtype avian influenza virus contributes to viral pathogenicity in mice.PLoS pathogens · 2023Article
- P21 facilitates macrophage chemotaxis by promoting CCL7 in the lung epithelial cell lines treated with radiation and bleomycin.Journal of translational medicine · 2023Article
- Phosphorylation of the PA subunit of influenza polymerase at Y393 prevents binding of the 5'-termini of RNA and polymerase function.Scientific reports · 2023Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 4 countries.
Funding
Abstract
Many cellular genes and networks induced in human lung epithelial cells infected with the influenza virus remain uncharacterized. Here, we find that p21 levels are elevated in response to influenza A virus (IAV) infection, which is independent of p53. Silencing, pharmacological inhibition or deletion of p21 promotes virus replication in vitro and in vivo, indicating that p21 is an influenza restriction factor. Mechanistically, p21 binds to the C-terminus of IAV polymerase subunit PA and competes with PB1 to limit IAV polymerase activity. Besides, p21 promotes IRF3 activation by blocking K48-linked ubiquitination degradation of HO-1 to enhance type I interferons expression. Furthermore, a synthetic p21 peptide (amino acids 36 to 43) significantly inhibits IAV replication in vitro and in vivo. Collectively, our findings reveal that p21 restricts IAV by perturbing the viral polymerase complex and activating the host innate immune response, which may aid the design of desperately needed new antiviral therapeutics.
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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 Socratic graph.