Fig. 3: Ongoing H5N1 outbreaks in cattle and other mammals have facilitated the emergence of additional mammalian-adapted mutations in PB2. | Nature Communications

Fig. 3: Ongoing H5N1 outbreaks in cattle and other mammals have facilitated the emergence of additional mammalian-adapted mutations in PB2.

From: Emergence of mammalian-adaptive PB2 mutations enhances polymerase activity and pathogenicity of cattle-derived H5N1 influenza A virus

Fig. 3: Ongoing H5N1 outbreaks in cattle and other mammals have facilitated the emergence of additional mammalian-adapted mutations in PB2.

A Variations of cow H5N1 PB2 amino acids. The PB2 sequences of H5N1 derived from dairy cows from 2024 to March 31, 2025 (n = 3,028) were aligned and compared for mutations. The horizontal axis represents amino acid positions on PB2, and the vertical axis shows the base-10 logarithm of mutation frequency. The notable mutations are marked. Four well-known mammal-adaptive mutations are highlighted in magenta. B Accumulation of representative H5N1 PB2 mutations derived from dairy cows. In the left panel, red denotes H5N1 genotype B3.13 (all bearing PB2 631L), while blue denotes H5N1 genotype D1.1 (all bearing PB2 631M). The right panel details the accumulation of key mutations in H5N1 B3.13. PB2 sequences are sorted by virus isolation date, with each column representing an individual viral isolate. Substitutions are highlighted in pink. Firefly luciferase reporter assay assessed the effects of the cow-related (C), nonhuman mammal-related (D) and human-related (E) mutations on cow H5N1 polymerase activity. 293T cells were co-transfected with plasmids expressing cowOH12-H5N1 PB2 (WT or mutant), PB1, PA, and NP proteins and a plasmid expressing firefly luciferase reporter vRNA. The relative polymerase activity was normalized to the wild-type (WT) cowPB2 group. Mutations that significantly enhanced polymerase activity are shown in red. Data are presented as mean values ± SD from n = 3 independent biological replicate experiments. Statistical significance was determined by one-way ANOVA with Dunnett’s post hoc test. Source Data are provided as a Source Data file.

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