Document detail
ID
oai:www.zora.uzh.ch:212971
Topic
Institute of Medical Virology 570 Life sciences biology 610 Medicine & healthAuthor
Lanz, Caroline Schotsaert, Michael Magnus, Carsten Karakus, Umut Hunziker, Annika Sempere Borau, Milagros Martínez-Romero, Carles Spieler, Eva E Günther, Sira C Moritz, Eva Hale, Benjamin G Trkola, Alexandra García-Sastre, Adolfo Stertz, SilkeLangue
engEditor
Rockefeller University Press
Category
Subjects = 04 Faculty of Medicine
Year
2021
listing date
10/12/2023
Keywords
iav ifitm3 antibody-mediated neutralization incorporation influenza virus haAbstract
The disease severity of influenza is highly variable in humans, and one genetic determinant behind these differences is the IFITM3 gene.
As an effector of the interferon response, IFITM3 potently blocks cytosolic entry of influenza A virus (IAV).
Here, we reveal a novel level of inhibition by IFITM3 in vivo: We show that incorporation of IFITM3 into IAV particles competes with incorporation of viral hemagglutinin (HA).
Decreased virion HA levels did not reduce infectivity, suggesting that high HA density on IAV virions may be an antagonistic strategy used by the virus to prevent direct inhibition.
However, we found that IFITM3-mediated reduction in HA content sensitizes IAV to antibody-mediated neutralization.
Mathematical modeling predicted that this effect decreases and delays peak IAV titers, and we show that, indeed, IFITM3-mediated sensitization of IAV to antibody-mediated neutralization impacts infection outcome in an in vivo mouse model.
Overall, our data describe a previously unappreciated interplay between the innate effector IFITM3 and the adaptive immune response.
Lanz, Caroline,Schotsaert, Michael,Magnus, Carsten,Karakus, Umut,Hunziker, Annika,Sempere Borau, Milagros,Martínez-Romero, Carles,Spieler, Eva E,Günther, Sira C,Moritz, Eva,Hale, Benjamin G,Trkola, Alexandra,García-Sastre, Adolfo,Stertz, Silke, 2021, IFITM3 incorporation sensitizes influenza A virus to antibody-mediated neutralization, Rockefeller University Press
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