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. 2025 Jan;31(1):199-202.
doi: 10.3201/eid3101.241236. Epub 2024 Dec 10.

Replication Restriction of Influenza A(H5N1) Clade 2.3.4.4b Viruses by Human Immune Factor, 2023-2024

Jakob Ankerhold, Susanne Kessler, Martin Beer, Martin Schwemmle, Kevin Ciminski

Replication Restriction of Influenza A(H5N1) Clade 2.3.4.4b Viruses by Human Immune Factor, 2023-2024

Jakob Ankerhold et al. Emerg Infect Dis. 2025 Jan.

Abstract

We show that human myxovirus resistance protein 1 (MxA) suppresses replication of highly pathogenic avian influenza A(H5N1) viruses isolated from mammals in vitro and in MxA-transgenic mice. However, H5N1 can evade MxA restriction through replacement of individual viral polymerase complex components from a human-adapted MxA-resistant strain in vitro.

Keywords: H5N1 clade 2.3.4.4b; MxA; highly pathogenic avian influenza A(H5N1) viruses; influenza; risk assessment; virus; viruses; zoonoses; zoonotic transmission.

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Figures

Figure 1
Figure 1
In vitro testing of replication of mammalian influenza A(H5N1) clade 2.3.4.4b isolates against human MxA. MDCK cells overexpressing MxA (MDCK-MxA) or antivirally inactive MxAT103A (MDCK-MxAT103A) were infected with an influenza A isolate at a multiplicity of infection of 0.001; viral titers were determined at the indicated time points. A) Pandemic H1N1. B) KAN-1 H5N1. C) White mink H5N1. D) Blue fox H5N1. E) Cat H5N1. F) Bovine H5N1. Data are mean ± SD of n = 3 independent experiments. Dashed line indicates detection limit. hpi, hours postinfection; MxA, human myxovirus resistance protein 1.
Figure 2
Figure 2
In vitro testing of bovine influenza A(H5N1) restriction through replacement of individual viral polymerase complex components from a human-adapted MxA-resistant strain. A) HEK293T cells were transfected with expression plasmids encoding the indicated pH1N1 or bovine H5N1 polymerase subunits PB2, PB1, PA, and NP together with expression plasmids encoding antivirally active MxA or the inactive MxAT103A variant. After 24 hours, we determined the relative polymerase activity as the ratio of MxA to MxAT103A. Data are mean ± SD of n = 4 independent experiments. B) HEK293T cells were transfected with expression plasmids encoding the pH1N1, KAN-1 H5N1, or bovine H5N1 polymerase subunits PB2, PB1, and PA together with the respective NP. After 24 hours, we determined the polymerase activity in presence of the indicated MxA/Mx1 variant, normalized to a transfection control, and calculated relative to the empty vector control. Data are mean ± SD of n = 4 independent experiments. We used 2-tailed t-tests for statistical analysis. MxA, human myxovirus resistance protein 1; NP, nucleoprotein; PA, polymerase; PB, polymerase basic; pH1N1, pandemic H1N1.
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