tetano
Editor, Senior Moderator
PLoS Pathog
. 2022 Feb 18;18(2):e1010295.
doi: 10.1371/journal.ppat.1010295. Online ahead of print.
p21 restricts influenza A virus by perturbing the viral polymerase complex and upregulating type I interferon signaling
Chao Ma[SUP] 1 [/SUP], Yuhan Li[SUP] 1 [/SUP], Yanan Zong[SUP] 1 [/SUP], Tony Velkov[SUP] 2 [/SUP], Chenxi Wang[SUP] 1 [/SUP], Xinyu Yang[SUP] 1 [/SUP], Ming Zhang[SUP] 3 [/SUP], Zhimin Jiang[SUP] 1 [/SUP], Haoran Sun[SUP] 1 [/SUP], Qi Tong[SUP] 1 [/SUP], Honglei Sun[SUP] 1 [/SUP], Juan Pu[SUP] 1 [/SUP], Munir Iqbal[SUP] 4 [/SUP], Jinhua Liu[SUP] 1 [/SUP], Chongshan Dai[SUP] 5 [/SUP], Yipeng Sun[SUP] 1 [/SUP]
Affiliations
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.
. 2022 Feb 18;18(2):e1010295.
doi: 10.1371/journal.ppat.1010295. Online ahead of print.
p21 restricts influenza A virus by perturbing the viral polymerase complex and upregulating type I interferon signaling
Chao Ma[SUP] 1 [/SUP], Yuhan Li[SUP] 1 [/SUP], Yanan Zong[SUP] 1 [/SUP], Tony Velkov[SUP] 2 [/SUP], Chenxi Wang[SUP] 1 [/SUP], Xinyu Yang[SUP] 1 [/SUP], Ming Zhang[SUP] 3 [/SUP], Zhimin Jiang[SUP] 1 [/SUP], Haoran Sun[SUP] 1 [/SUP], Qi Tong[SUP] 1 [/SUP], Honglei Sun[SUP] 1 [/SUP], Juan Pu[SUP] 1 [/SUP], Munir Iqbal[SUP] 4 [/SUP], Jinhua Liu[SUP] 1 [/SUP], Chongshan Dai[SUP] 5 [/SUP], Yipeng Sun[SUP] 1 [/SUP]
Affiliations
- PMID: 35180274
- DOI: 10.1371/journal.ppat.1010295
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.