Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Interactions between influenza A virus nucleoprotein and gene segment UTRs facilitate selective modulation of viral gene expression

Meghan Diefenbacher, View ORCID ProfileTimothy JC Tan, David LV Bauer, View ORCID ProfileBeth Stadtmueller, View ORCID ProfileNicholas C. Wu, View ORCID ProfileChristopher B. Brooke
doi: https://doi.org/10.1101/2022.01.09.475567
Meghan Diefenbacher
1Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Timothy JC Tan
2Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Timothy JC Tan
David LV Bauer
3RNA Virus Replication Laboratory, The Francis Crick Institute, London, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Beth Stadtmueller
4Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America
5Department of Biomedical and Translational Sciences, Carle Illinois College of Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Beth Stadtmueller
Nicholas C. Wu
2Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America
4Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America
5Department of Biomedical and Translational Sciences, Carle Illinois College of Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America
6Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Nicholas C. Wu
Christopher B. Brooke
1Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America
6Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Christopher B. Brooke
  • For correspondence: cbrooke@illinois.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

The influenza A virus (IAV) genome is divided into eight negative-sense, single-stranded RNA segments. Each segment exhibits a unique level and temporal pattern of expression, however the exact mechanisms underlying the patterns of individual gene segment expression are poorly understood. We previously demonstrated that a single substitution in the viral nucleoprotein (NP:F346S) selectively modulates neuraminidase (NA) gene segment expression while leaving other segments largely unaffected. Given what is currently known about NP function, there is no obvious explanation for how changes in NP can selectively modulate the replication of individual gene segments. We found that the specificity of this effect for the NA segment is virus strain specific and depends on the UTR sequences of the NA segment. While the NP:F346S substitution did not significantly alter the RNA binding or oligomerization activities of NP in vitro, it specifically decreased the ability of NP to promote NA segment vRNA synthesis. In addition to NP residue F346, we identified two other adjacent aromatic residues in NP (Y385 & F479) capable of similarly regulating NA gene segment expression, suggesting a larger role for this domain in gene-segment specific regulation. Our findings reveal a new role for NP in selective regulation of viral gene segment replication and demonstrate how the expression patterns of individual viral gene segments can be modulated during adaptation to new host environments.

Author summary Influenza A virus (IAV) is a respiratory pathogen that remains a significant source of morbidity and mortality. Escape from host immunity or emergence into new host species often requires mutations that modulate the functional activities of the viral glycoproteins hemagglutinin (HA) and neuraminidase (NA) which are responsible for virus attachment to and release from host cells, respectively. Maintaining the functional balance between the activities of HA and NA is required for fitness across multiple host systems. Thus, selective modulation of viral gene expression patterns may be a key determinant of viral immune escape and cross-species transmission potential. We identified a novel mechanism by which the viral nucleoprotein (NP) gene can selectively modulate NA segment replication and gene expression through interactions with the segment UTR. Our work highlights an unexpected role for NP in selective regulation of expression from the individual IAV gene segments.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • corrected author name spelling/capitalization

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted January 11, 2022.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Interactions between influenza A virus nucleoprotein and gene segment UTRs facilitate selective modulation of viral gene expression
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Interactions between influenza A virus nucleoprotein and gene segment UTRs facilitate selective modulation of viral gene expression
Meghan Diefenbacher, Timothy JC Tan, David LV Bauer, Beth Stadtmueller, Nicholas C. Wu, Christopher B. Brooke
bioRxiv 2022.01.09.475567; doi: https://doi.org/10.1101/2022.01.09.475567
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Interactions between influenza A virus nucleoprotein and gene segment UTRs facilitate selective modulation of viral gene expression
Meghan Diefenbacher, Timothy JC Tan, David LV Bauer, Beth Stadtmueller, Nicholas C. Wu, Christopher B. Brooke
bioRxiv 2022.01.09.475567; doi: https://doi.org/10.1101/2022.01.09.475567

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Microbiology
Subject Areas
All Articles
  • Animal Behavior and Cognition (3513)
  • Biochemistry (7358)
  • Bioengineering (5334)
  • Bioinformatics (20290)
  • Biophysics (10032)
  • Cancer Biology (7753)
  • Cell Biology (11323)
  • Clinical Trials (138)
  • Developmental Biology (6442)
  • Ecology (9962)
  • Epidemiology (2065)
  • Evolutionary Biology (13340)
  • Genetics (9363)
  • Genomics (12594)
  • Immunology (7717)
  • Microbiology (19055)
  • Molecular Biology (7452)
  • Neuroscience (41085)
  • Paleontology (300)
  • Pathology (1232)
  • Pharmacology and Toxicology (2140)
  • Physiology (3169)
  • Plant Biology (6867)
  • Scientific Communication and Education (1275)
  • Synthetic Biology (1899)
  • Systems Biology (5320)
  • Zoology (1089)