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Comprehensive Evolutionary and Structural Analysis of the H5N1 Clade 2.4.3.4b Influenza a Virus Based on the Sequences and Data Mining of the Hemagglutinin, Nucleoprotein and Neuraminidase Genes Across Multiple Hosts
 
 
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Pathogens
Volume 14
Issue 9
10.3390/pathogens14090929
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Review
Peer-Review Record

H5N1 Clade 2.3.4.4b: Evolution, Global Spread, and Host Range Expansion

Pathogens 2025, 14(9), 929; https://doi.org/10.3390/pathogens14090929
by Klaudia Chrzastek 1,*, Carolin M. Lieber 2 and Richard K. Plemper 2
Reviewer 1: Anonymous
Reviewer 2: Anonymous
Pathogens 2025, 14(9), 929; https://doi.org/10.3390/pathogens14090929
Submission received: 18 August 2025 / Revised: 8 September 2025 / Accepted: 9 September 2025 / Published: 15 September 2025
(This article belongs to the Special Issue Emerging and Re-Emerging Avian Influenza Viruses in Wildlife)

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This manuscript is a review of H5N1 genetic evolution and geographic spread and broadened host species.  The review provided excellent detail of the H5N1 early history and its evolution to this day. The manuscript was clearly written providing adequate detail with clear subsections. Nevertheless, there are minor revisions that should be addressed:

1) Line 29 - there are now 18 different HA subtypes, not 16.  This should be corrected.

2) Line 119 - I believe the authors meant "local viruses (led) to a.." and not (let). This needs to be corrected.

3) Line 119-120.  There should be a reference cited for the statement "Reassortment events between H5N8 and circulation....subtype from H5N8 to H5N1 in 2021".

4) Line 439-443 should be rephrased.  It is quite awkwardly written at present.

5) Line 449- The subsection "Recent Human Cases" indicates a coverage between 2022 to 2025 but only reported data up to 2023.  Data for 2024 and 2025 should be included here. The authors should ensure that they are consistent throughout the manuscript to cover the indicated range of time.

 

Author Response

The authors would like to thank the reviewer for the insightful comments and suggestions. We have carefully revised the manuscript accordingly. Our responses are provided below:

  1. Line 29 – The statement regarding the number of HA subtypes has been corrected to reflect 18 subtypes instead of 16.

  2. Line 119 – The wording has been corrected from "let" to "led" as suggested.

  3. Lines 119–120 – A proper reference has now been included for the statement regarding reassortment events between H5N8 and circulating subtypes leading to the emergence of H5N1 in 2021.

  4. Lines 439–443 – This section has been re-written to improve clarity and readability.

  5. Line 449, subsection "Recent Human Cases" – We have revised the section to ensure consistency with the stated coverage period (2022–2025) by including updated information on human cases reported in 2024 and 2025.

Reviewer 2 Report

Comments and Suggestions for Authors

As per the attached file

Comments for author File: Comments.pdf

Author Response

The authors would like to thank the reviewer for the valuable feedback. We have carefully revised the manuscript according to the suggestions. Specifically, we have added the missing references and corrected the text as recommended. In addition, although it was not explicitly requested, we also included more updated information on current cases to further strengthen the manuscript.

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