Abstract

Influenza is an acute respiratory infection causing high morbidity and mortality in annual outbreaks worldwide. Antiviral drugs are limited and pose the risk of resistance development, calling for new treatment options. IFN-α subtypes are immune-stimulatory cytokines with strong antiviral activities against IAV in vitro and in vivo. However, the clinical use of IFN-α2, the only licensed subtype of this multi-gene family, could not prevent or limit IAV infections in humans. However, the other subtypes were not investigated.

Therefore, this study evaluated the induction and antiviral potential of all human IFN-α subtypes during H3N2 IAV infection in human lung explants. We found that subtypes with weak antiviral activities were preferentially induced during IAV infection in human lungs. Intriguingly, non-induced subtypes α16, α5 and α4 suppressed viral replication up to 230-fold more efficiently than α2. Furthermore, our results demonstrate that subtypes with stronger antiviral activities induce higher expression of IAV-specific restriction factors and that MxA expression is a determinant of the subtype-specific antiviral activity towards H3N2 IAV. These results corroborate that IFN-α subtypes exhibit differential antiviral activities and emphasize that subtypes α16, α5 and α4 should be further investigated for the prevention and treatment of severe infections with seasonal H3N2 IAV.

Details

Title
Antiviral potential of human IFN-α subtypes against influenza A H3N2 infection in human lung explants reveals subtype-specific activities
Author
Aline da Rocha Matos 1 ; Wunderlich, Katharina 2 ; Schloer, Sebastian 3 ; Schughart, Klaus 4 ; Geffers, Robert 5 ; Seders, Martine 2 ; de Witt, Marlous 2 ; Christersson, Anmari 2 ; Wiewrodt, Rainer 6 ; Wiebe, Karsten 7 ; Barth, Peter 8 ; Hocke, Andreas 9 ; Hippenstiel, Stefan 9 ; Hönzke, Katja 9 ; Dittmer, Ulf 10 ; Sutter, Kathrin 10 ; Rescher, Ursula 3 ; Rodionycheva, Svetlana 7 ; Matera, Nicoletta 7 ; Ludwig, Stephan 2   VIAFID ORCID Logo  ; Brunotte, Linda 2   VIAFID ORCID Logo 

1  Institute of Virology Muenster, Westfaelische Wilhelms-University, Muenster, Germany; Respiratory Viruses and Measles Lab, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil 
2  Institute of Virology Muenster, Westfaelische Wilhelms-University, Muenster, Germany 
3  Institute of Medical Biochemistry, Westfaelische Wilhelms-University, Muenster, Germany 
4  Department of Infection Genetics, Helmholtz Centre for Infection Research, Braunschweig, Germany 
5  Genome analytics, Helmholtz Centre for Infection Research, Braunschweig, Germany 
6  Department of Medicine A, Hematology, Oncology and Respiratory Medicine, University Hospital Muenster, Muenster, Germany 
7  Department of Thoracic Surgery, University Hospital Muenster, Muenster, Germany 
8  Gerhard-Domagk-Institute of Pathology, Westfaelische Wilhelms-University, Muenster, Germany 
9  Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Internal Medicine/Infectious Diseases and Respiratory Medicine, Berlin, Germany 
10  Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Duisburg, Germany 
Pages
1763-1776
Publication year
2019
Publication date
2019
Publisher
Taylor & Francis Ltd.
e-ISSN
22221751
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1080/22221751.2019.1698271
ProQuest document ID
2427525650
Copyright
© 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd. This work is licensed under the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.