Research Article

Phylogenetic distribution of PB2 E627K and D701N mutations in global H5N1 influenza A viruses

Volume: 10 Number: 2 September 15, 2026

Phylogenetic distribution of PB2 E627K and D701N mutations in global H5N1 influenza A viruses

Abstract

Objective: This study investigates the phylogenetic distribution of the mammalian adaptation–associated E627K and D701N mutations in the PB2 gene of H5N1 influenza A virus. It aims to determine whether these substitutions cluster within specific viral lineages or arise independently across distinct genetic backgrounds. Materials and Methods: We retrieved 1,870 global PB2 sequences of H5N1 influenza A virus from publicly accessible databases, including 169 human-derived isolates. The sequences were aligned using multiple sequence alignment, and phylogenetic reconstruction was performed using the Maximum Likelihood method under the best-fit nucleotide substitution model. The presence of E627K and D701N amino acid substitutions in the PB2 protein was identified through translation analysis and mapped onto the phylogenetic tree. Host origin (avian vs. human/mammalian) was recorded and incorporated into the analysis to assess mutation–host associations. Results: Phylogenetic analysis revealed that E627K substitutions exhibited lineage-associated clustering, with mutation-enriched subclades containing a considerable proportion of human-derived isolates. This pattern suggests clade-related expansion following acquisition of the adaptive mutation. In contrast, D701N substitutions showed a more scattered distribution across the phylogenetic tree, indicating multiple independent emergence events consistent with parallel evolution. Human-derived isolates were not restricted to a single evolutionary lineage, demonstrating that mammalian-adaptive mutations can arise across diverse viral genetic backgrounds. Conclusions: The evolutionary dynamics of PB2 adaptive mutations in H5N1 reflect both clade-associated expansion and recurrent parallel emergence. These findings highlight the considerable adaptive flexibility of H5N1 and emphasize the importance of continuous genomic surveillance to improve zoonotic risk assessment and early detection of mammalian-adapted variants.

Keywords

Ethical Statement

Ethical approval is not required, as this study is based solely on the analysis of sequences obtained from publicly available databases and does not involve any human or animal experiments.

References

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Details

Primary Language

English

Subjects

Veterinary Epidemiology, Veterinary Medicine, Veterinary Virology

Journal Section

Research Article

Publication Date

September 15, 2026

Submission Date

April 6, 2026

Acceptance Date

July 23, 2026

Published in Issue

Year 2026 Volume: 10 Number: 2

APA
Ekici, S., Dülger, D., Demirci, M., Gürkök Tan, T., & Akçay, S. (2026). Phylogenetic distribution of PB2 E627K and D701N mutations in global H5N1 influenza A viruses. Turkish Journal of Veterinary Research, 10(2). https://doi.org/10.47748/tjvr.1924007
AMA
1.Ekici S, Dülger D, Demirci M, Gürkök Tan T, Akçay S. Phylogenetic distribution of PB2 E627K and D701N mutations in global H5N1 influenza A viruses. TJVR. 2026;10(2). doi:10.47748/tjvr.1924007
Chicago
Ekici, Seda, Dilek Dülger, Mehmet Demirci, Tuğba Gürkök Tan, and Sevinç Akçay. 2026. “Phylogenetic Distribution of PB2 E627K and D701N Mutations in Global H5N1 Influenza A Viruses”. Turkish Journal of Veterinary Research 10 (2). https://doi.org/10.47748/tjvr.1924007.
EndNote
Ekici S, Dülger D, Demirci M, Gürkök Tan T, Akçay S (September 1, 2026) Phylogenetic distribution of PB2 E627K and D701N mutations in global H5N1 influenza A viruses. Turkish Journal of Veterinary Research 10 2
IEEE
[1]S. Ekici, D. Dülger, M. Demirci, T. Gürkök Tan, and S. Akçay, “Phylogenetic distribution of PB2 E627K and D701N mutations in global H5N1 influenza A viruses”, TJVR, vol. 10, no. 2, Sept. 2026, doi: 10.47748/tjvr.1924007.
ISNAD
Ekici, Seda - Dülger, Dilek - Demirci, Mehmet - Gürkök Tan, Tuğba - Akçay, Sevinç. “Phylogenetic Distribution of PB2 E627K and D701N Mutations in Global H5N1 Influenza A Viruses”. Turkish Journal of Veterinary Research 10/2 (September 1, 2026). https://doi.org/10.47748/tjvr.1924007.
JAMA
1.Ekici S, Dülger D, Demirci M, Gürkök Tan T, Akçay S. Phylogenetic distribution of PB2 E627K and D701N mutations in global H5N1 influenza A viruses. TJVR. 2026;10. doi:10.47748/tjvr.1924007.
MLA
Ekici, Seda, et al. “Phylogenetic Distribution of PB2 E627K and D701N Mutations in Global H5N1 Influenza A Viruses”. Turkish Journal of Veterinary Research, vol. 10, no. 2, Sept. 2026, doi:10.47748/tjvr.1924007.
Vancouver
1.Seda Ekici, Dilek Dülger, Mehmet Demirci, Tuğba Gürkök Tan, Sevinç Akçay. Phylogenetic distribution of PB2 E627K and D701N mutations in global H5N1 influenza A viruses. TJVR. 2026 Sep. 1;10(2). doi:10.47748/tjvr.1924007