Acetylation of the influenza A virus polymerase subunit PA in the N ‐terminal domain positively regulates its endonuclease activity

FEBS Journal ◽  
2021 ◽  
Author(s):  
Dai Hatakeyama ◽  
Masaki Shoji ◽  
Seiryo Ogata ◽  
Takeshi Masuda ◽  
Masahiro Nakano ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Endonuclease Activity ◽  
Terminal Domain

scholarly journals Protective role for the N-terminal domain of α-dystroglycan in Influenza A virus proliferation

2019 ◽  
Vol 116 (23) ◽  
pp. 11396-11401 ◽  
Author(s):  
Jessica C. de Greef ◽  
Bram Slütter ◽  
Mary E. Anderson ◽  
Rebecca Hamlyn ◽  
Raul O’Campo Landa ◽  
...  
Keyword(s):  
Puerto Rico ◽  
Basement Membrane ◽  
Influenza A Virus ◽  
Influenza A ◽  
Protective Role ◽  
Wild Type ◽  
Terminal Domain ◽  
Bodily Fluids ◽  
Control Virus

α-Dystroglycan (α-DG) is a highly glycosylated basement membrane receptor that is cleaved by the proprotein convertase furin, which releases its N-terminal domain (α-DGN). Before cleavage, α-DGN interacts with the glycosyltransferase LARGE1 and initiates functional O-glycosylation of the mucin-like domain of α-DG. Notably, α-DGN has been detected in a wide variety of human bodily fluids, but the physiological significance of secreted α-DGN remains unknown. Here, we show that mice lacking α-DGN exhibit significantly higher viral titers in the lungs after Influenza A virus (IAV) infection (strain A/Puerto Rico/8/1934 H1N1), suggesting an inability to control virus load. Consistent with this, overexpression of α-DGN before infection or intranasal treatment with recombinant α-DGN prior and during infection, significantly reduced IAV titers in the lungs of wild-type mice. Hemagglutination inhibition assays using recombinant α-DGN showed in vitro neutralization of IAV. Collectively, our results support a protective role for α-DGN in IAV proliferation.

scholarly journals EPR Spectroscopy of the C-terminal Domain of the M2 Protein from Influenza A Virus

2009 ◽  
Vol 96 (3) ◽  
pp. 432a
Author(s):  
Emily Brown ◽  
Phuong Nguyen ◽  
Kathleen P. Howard
Keyword(s):  
Influenza A Virus ◽  
Epr Spectroscopy ◽  
Influenza A ◽  
M2 Protein ◽  
Terminal Domain

scholarly journals Cross-Protection of Influenza A Virus Infection by a DNA Aptamer Targeting the PA Endonuclease Domain

2015 ◽  
Vol 59 (7) ◽  
pp. 4082-4093 ◽  
Author(s):  
Shuofeng Yuan ◽  
Naru Zhang ◽  
Kailash Singh ◽  
Huiping Shuai ◽  
Hin Chu ◽  
...  
Keyword(s):  
Virus Infection ◽  
Influenza A Virus ◽  
Influenza A ◽  
H5n1 Virus ◽  
Influenza Viruses ◽  
Cross Protection ◽  
Dna Aptamer ◽  
Endonuclease Activity ◽  
Endonuclease Domain

ABSTRACTAmino acid residues in the N-terminal of the PA subunit (PAN) of the influenza A virus polymerase play critical roles in endonuclease activity, protein stability, and viral RNA (vRNA) promoter binding. In addition, PANis highly conserved among different subtypes of influenza virus, which suggests PANto be a desired target in the development of anti-influenza agents. We selected DNA aptamers targeting the intact PA protein or the PANdomain of an H5N1 virus strain using systematic evolution of ligands by exponential enrichment (SELEX). The binding affinities of selected aptamers were measured, followed by an evaluation ofin vitroendonuclease inhibitory activity. Next, the antiviral effects of enriched aptamers against influenza A virus infections were examined. A total of three aptamers targeting PA and six aptamers targeting PANwere selected. Our data demonstrated that all three PA-selected aptamers neither inhibited endonuclease activity nor exhibited antiviral efficacy, whereas four of the six PAN-selected aptamers inhibited both endonuclease activity and H5N1 virus infection. Among the four effective aptamers, one exhibited cross-protection against infections of H1N1, H5N1, H7N7, and H7N9 influenza viruses, with a 50% inhibitory concentration (IC50) of around 10 nM. Notably, this aptamer was identified at the 5th round but disappeared after the 10th round of selection, suggesting that the identification and evaluation of aptamers at early rounds of selection may be highly helpful for screening effective aptamers. Overall, our study provides novel insights for screening and developing effective aptamers for use as anti-influenza drugs.

A novel function of the N-terminal domain of PA in assembly of influenza A virus RNA polymerase

2011 ◽  
Vol 414 (4) ◽  
pp. 719-726 ◽  
Author(s):  
Tadaki Suzuki ◽  
Akira Ainai ◽  
Noriyo Nagata ◽  
Tetsutaro Sata ◽  
Hirofumi Sawa ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Influenza A Virus ◽  
Influenza A ◽  
Terminal Domain ◽  
Virus Rna

scholarly journals Mutagenic Analysis of the 5′ Arm of the Influenza A Virus Virion RNA Promoter Defines the Sequence Requirements for Endonuclease Activity

2001 ◽  
Vol 75 (1) ◽  
pp. 134-142 ◽  
Author(s):  
Michael B. Leahy ◽  
David C. Pritlove ◽  
Leo L. M. Poon ◽  
George G. Brownlee
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Influenza A ◽  
Endonuclease Activity ◽  
Hairpin Loop ◽  
Promoter Sequences ◽  
Sequence Requirements ◽  
Rna Promoter ◽  
Virus Promoter

ABSTRACT Short synthetic influenza virus-like RNAs derived from influenza virus promoter sequences were examined for their ability to stimulate the endonuclease activity of recombinant influenza virus polymerase complexes in vitro, an activity that is required for the cap-snatching activity of primers from host pre-mRNA. An extensive set of point mutants of the 5′ arm of the influenza A virus viral RNA (vRNA) was constructed to determine the cis-acting elements which influenced endonuclease activity. Activity was found to be dependent on three features of the conserved vRNA termini: (i) the presence of the 5′ hairpin loop structure, (ii) the identity of residues at positions 5 and 10 bases from the 5′ terminus, and (iii) the presence of base pair interactions between the 5′ and 3′ segment ends. Further experiments discounted a role for the vRNA U track in endonuclease activation. This study represents the first mutagenic analysis of the influenza virus promoter with regard to endonuclease activity.

scholarly journals N-terminal domain of PB1-F2 protein of influenza A virus can fold into amyloid-like oligomers and damage cholesterol and cardiolipid containing membranes

2016 ◽  
Vol 477 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Dalila Ajjaji ◽  
Charles-Adrien Richard ◽  
Sandra Mazerat ◽  
Christophe Chevalier ◽  
Jasmina Vidic
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Terminal Domain

scholarly journals A crucial role of N-terminal domain of influenza A virus M1 protein in interaction with swine importin α1 protein

Virus Genes ◽  
2014 ◽  
Vol 49 (1) ◽  
pp. 157-162 ◽  
Author(s):  
Qinfang Liu ◽  
Bhupinder Bawa ◽  
Jingjiao Ma ◽  
Feng Li ◽  
Wenjun Ma ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Crucial Role ◽  
Influenza A ◽  
Terminal Domain ◽  
M1 Protein

scholarly journals The native structure of the full-length, assembled influenza A virus matrix protein, M1

2020 ◽  
Author(s):  
Julia Peukes ◽  
Xiaoli Xiong ◽  
Simon Erlendsson ◽  
Kun Qu ◽  
William Wan ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Matrix Protein ◽  
Virus Assembly ◽  
Full Length ◽  
Terminal Domain ◽  
Intact Virus ◽  
The Matrix ◽  
Matrix Protein M1

Influenza A virus causes millions of severe illnesses during annual epidemics. The most abundant protein in influenza virions is the matrix protein M1 that mediates virus assembly by forming an endoskeleton beneath the virus membrane. The structure of full-length M1, and how it oligomerizes to mediate assembly of virions, is unknown. Here we have determined the complete structure of assembled M1 within intact virus particles, as well as the structure of M1 oligomers reconstituted in vitro. We found that the C-terminal domain of M1 is disordered in solution, but can fold and bind in trans to the N-terminal domain of another M1 monomer, thus polymerising M1 into linear strands which coat the interior surface of the assembling virion membrane. In the M1 polymer, five histidine residues, contributed by three different M1 monomers, form a cluster that can serve as the pH-sensitive disassembly switch after entry into a target cell. These structures therefore provide mechanisms for influenza virus assembly and disassembly.

Total Chemical Synthesis of the Integral Membrane Protein Influenza A Virus M2:  Role of Its C-Terminal Domain in Tetramer Assembly†

Biochemistry ◽  
1999 ◽  
Vol 38 (37) ◽  
pp. 11905-11913 ◽  
Author(s):  
Gerd G. Kochendoerfer ◽  
David Salom ◽  
James D. Lear ◽  
Rosemarie Wilk-Orescan ◽  
Stephen B. H. Kent ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Chemical Synthesis ◽  
Influenza A Virus ◽  
Influenza A ◽  
Integral Membrane Protein ◽  
Terminal Domain
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