Exchange of amino acids in the H1-haemagglutinin to H3 residues is required for efficient influenza A virus replication and pathology in Tmprss2 knock-out mice.
Average rating
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Star rating
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Authors
Lambertz, Ruth L OPippel, Jan
Gerhauser, Ingo
Kollmus, Heike
Anhlan, Darisuren
Hrincius, Eike R
Krausze, Joern
Kühn, Nora
Schughart, Klaus
Issue Date
2018-09-01
Metadata
Show full item recordAbstract
The haemagglutinin (HA) of H1N1 and H3N2 influenza A virus (IAV) subtypes has to be activated by host proteases. Previous studies showed that H1N1 virus cannot replicate efficiently in Tmprss2/ knock-out mice whereas H3N2 viruses are able to replicate to the same levels in Tmprss2/ as in wild type (WT) mice. Here, we investigated the sequence requirements for the HA molecule that allow IAV to replicate efficiently in the absence of TMPRSS2. We showed that replacement of the H3 for the H1-loop sequence (amino acids 320 to 329, at the C-terminus of HA1) was not sufficient for equal levels of virus replication or severe pathology in Tmprss2/ knock-out mice compared to WT mice. However, exchange of a distant amino acid from H1 to H3 sequence (E31D) in addition to the HA-loop substitution resulted in virus replication in Tmprss2/ knockout mice that was comparable to WT mice. The higher virus replication and lung damage was associated with increased epithelial damage and higher mortality. Our results provide further evidence and insights into host proteases as a promising target for therapeutic intervention of IAV infections.Affiliation
Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.PubMed ID
30084768Type
ArticleISSN
1465-2099ae974a485f413a2113503eed53cd6c53
10.1099/jgv.0.001128
Scopus Count
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 3.0 United States
Related articles
- Hemagglutinins of Avian Influenza Viruses Are Proteolytically Activated by TMPRSS2 in Human and Murine Airway Cells.
- Authors: Bestle D, Limburg H, Kruhl D, Harbig A, Stein DA, Moulton H, Matrosovich M, Abdelwhab EM, Stech J, Böttcher-Friebertshäuser E
- Issue date: 2021 Sep 27
- Transcriptome profiling and protease inhibition experiments identify proteases that activate H3N2 influenza A and influenza B viruses in murine airways.
- Authors: Harbig A, Mernberger M, Bittel L, Pleschka S, Schughart K, Steinmetzer T, Stiewe T, Nist A, Böttcher-Friebertshäuser E
- Issue date: 2020 Aug 14
- TMPRSS2 Is the Major Activating Protease of Influenza A Virus in Primary Human Airway Cells and Influenza B Virus in Human Type II Pneumocytes.
- Authors: Limburg H, Harbig A, Bestle D, Stein DA, Moulton HM, Jaeger J, Janga H, Hardes K, Koepke J, Schulte L, Koczulla AR, Schmeck B, Klenk HD, Böttcher-Friebertshäuser E
- Issue date: 2019 Nov 1
- TMPRSS2 is a host factor that is essential for pneumotropism and pathogenicity of H7N9 influenza A virus in mice.
- Authors: Tarnow C, Engels G, Arendt A, Schwalm F, Sediri H, Preuss A, Nelson PS, Garten W, Klenk HD, Gabriel G, Böttcher-Friebertshäuser E
- Issue date: 2014 May
- The Proteolytic Activation of (H3N2) Influenza A Virus Hemagglutinin Is Facilitated by Different Type II Transmembrane Serine Proteases.
- Authors: Kühn N, Bergmann S, Kösterke N, Lambertz RLO, Keppner A, van den Brand JMA, Pöhlmann S, Weiß S, Hummler E, Hatesuer B, Schughart K
- Issue date: 2016 May