tetano
Editor, Senior Moderator
Emerg Microbes Infect. 2019;8(1):1763-1776. doi: 10.1080/22221751.2019.1698271. [h=1]Antiviral potential of human IFN-α subtypes against influenza A H3N2 infection in human lung explants reveals subtype-specific activities.[/h]
Matos ADR[SUP]1,[/SUP][SUP]2[/SUP], Wunderlich K[SUP]1[/SUP], Schloer S[SUP]3[/SUP], Schughart K[SUP]4[/SUP], Geffers R[SUP]5[/SUP], Seders M[SUP]1[/SUP], Witt M[SUP]1[/SUP], Christersson A[SUP]1[/SUP], Wiewrodt R[SUP]6[/SUP], Wiebe K[SUP]7[/SUP], Barth P[SUP]8[/SUP], Hocke A[SUP]9[/SUP], Hippenstiel S[SUP]9[/SUP], H?nzke K[SUP]9[/SUP], Dittmer U[SUP]10[/SUP], Sutter K[SUP]10[/SUP], Rescher U[SUP]3[/SUP], Rodionycheva S[SUP]7[/SUP], Matera N[SUP]7[/SUP], Ludwig S[SUP]1[/SUP], Brunotte L[SUP]1[/SUP].
[h=3]Author information[/h] 1 Institute of Virology Muenster, Westfaelische Wilhelms-University, Muenster, Germany. 2 Respiratory Viruses and Measles Lab, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil. 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 Charit? - Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin, Humboldt-Universit?t 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.
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] Human lung explant; IFN-α subtype; ISG induction; MxA; antiviral; influenza
PMID: 31826721 DOI: 10.1080/22221751.2019.1698271
Matos ADR[SUP]1,[/SUP][SUP]2[/SUP], Wunderlich K[SUP]1[/SUP], Schloer S[SUP]3[/SUP], Schughart K[SUP]4[/SUP], Geffers R[SUP]5[/SUP], Seders M[SUP]1[/SUP], Witt M[SUP]1[/SUP], Christersson A[SUP]1[/SUP], Wiewrodt R[SUP]6[/SUP], Wiebe K[SUP]7[/SUP], Barth P[SUP]8[/SUP], Hocke A[SUP]9[/SUP], Hippenstiel S[SUP]9[/SUP], H?nzke K[SUP]9[/SUP], Dittmer U[SUP]10[/SUP], Sutter K[SUP]10[/SUP], Rescher U[SUP]3[/SUP], Rodionycheva S[SUP]7[/SUP], Matera N[SUP]7[/SUP], Ludwig S[SUP]1[/SUP], Brunotte L[SUP]1[/SUP].
[h=3]Author information[/h] 1 Institute of Virology Muenster, Westfaelische Wilhelms-University, Muenster, Germany. 2 Respiratory Viruses and Measles Lab, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil. 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 Charit? - Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin, Humboldt-Universit?t 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.
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] Human lung explant; IFN-α subtype; ISG induction; MxA; antiviral; influenza
PMID: 31826721 DOI: 10.1080/22221751.2019.1698271