Bat-borne H9N2 influenza virus evades MxA restriction and exhibits efficient replication and transmission in ferrets

Nico Joel Halwe, Lea Hamberger, Julia Sehl-Ewert, Christin Mache, Jacob Schön, Lorenz Ulrich, Sten Calvelage, Mario Tönnies, Jonas Fuchs, Pooja Bandawane, Madhumathi Loganathan, Anass Abbad, Juan Manuel Carreño, Maria C. Bermúdez-González, Viviana Simon, Ahmed Kandeil, Rabeh El-Shesheny, Mohamed A. Ali, Ghazi Kayali, Matthias Budt, Stefan Hippenstiel, Andreas C. Hocke, Florian Krammer, Thorsten Wolff, Martin Schwemmle, Kevin Ciminski (), Donata Hoffmann () and Martin Beer ()
Additional contact information
Nico Joel Halwe: Friedrich-Loeffler-Institut
Lea Hamberger: Medical Center-University of Freiburg
Julia Sehl-Ewert: Friedrich-Loeffler-Institut
Christin Mache: Robert Koch-Institut
Jacob Schön: Friedrich-Loeffler-Institut
Lorenz Ulrich: Friedrich-Loeffler-Institut
Sten Calvelage: Friedrich-Loeffler-Institut
Mario Tönnies: Chest Hospital Heckeshorn
Jonas Fuchs: Medical Center-University of Freiburg
Pooja Bandawane: Icahn School of Medicine at Mount Sinai
Madhumathi Loganathan: Icahn School of Medicine at Mount Sinai
Anass Abbad: Icahn School of Medicine at Mount Sinai
Juan Manuel Carreño: Icahn School of Medicine at Mount Sinai
Maria C. Bermúdez-González: Icahn School of Medicine at Mount Sinai
Viviana Simon: Icahn School of Medicine at Mount Sinai
Ahmed Kandeil: Institute of Environmental Research and Climate Changes, National Research Centre
Rabeh El-Shesheny: Institute of Environmental Research and Climate Changes, National Research Centre
Mohamed A. Ali: Institute of Environmental Research and Climate Changes, National Research Centre
Ghazi Kayali: Institute of Environmental Research and Climate Changes, National Research Centre
Matthias Budt: Robert Koch-Institut
Stefan Hippenstiel: Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin
Andreas C. Hocke: Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin
Florian Krammer: Icahn School of Medicine at Mount Sinai
Thorsten Wolff: Robert Koch-Institut
Martin Schwemmle: Medical Center-University of Freiburg
Kevin Ciminski: Medical Center-University of Freiburg
Donata Hoffmann: Friedrich-Loeffler-Institut
Martin Beer: Friedrich-Loeffler-Institut

Nature Communications, 2024, vol. 15, issue 1, 1-8

Abstract: Abstract Influenza A viruses (IAVs) of subtype H9N2 have reached an endemic stage in poultry farms in the Middle East and Asia. As a result, human infections with avian H9N2 viruses have been increasingly reported. In 2017, an H9N2 virus was isolated for the first time from Egyptian fruit bats (Rousettus aegyptiacus). Phylogenetic analyses revealed that bat H9N2 is descended from a common ancestor dating back centuries ago. However, the H9 and N2 sequences appear to be genetically similar to current avian IAVs, suggesting recent reassortment events. These observations raise the question of the zoonotic potential of the mammal-adapted bat H9N2. Here, we investigate the infection and transmission potential of bat H9N2 in vitro and in vivo, the ability to overcome the antiviral activity of the human MxA protein, and the presence of N2-specific cross-reactive antibodies in human sera. We show that bat H9N2 has high replication and transmission potential in ferrets, efficiently infects human lung explant cultures, and is able to evade antiviral inhibition by MxA in transgenic B6 mice. Together with its low antigenic similarity to the N2 of seasonal human strains, bat H9N2 fulfils key criteria for pre-pandemic IAVs.

Date: 2024
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DOI: 10.1038/s41467-024-47455-6

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