Peer Review History

Original SubmissionNovember 16, 2021

Attachments
Attachment
Submitted filename: Rebuttal letter_submission.docx
Decision Letter - Marco Vignuzzi, Editor

Dear Prof. Murcia,

Thank you very much for submitting your manuscript "Long-term adaptation following influenza A virus host shifts results in increased within-host viral fitness due to higher replication rates, broader dissemination within the respiratory epithelium and reduced tissue damage" for consideration at PLOS Pathogens. Your manuscript was reviewed by members of the editorial board and by the reviewers of the original submission. Based on the reviews, we are likely to accept this manuscript for publication, providing that you make further minor modifications as recommended.

Please prepare and submit your revised manuscript within 30 days. If you anticipate any delay, please let us know the expected resubmission date by replying to this email.

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[1] A letter containing a detailed list of your responses to all review comments, and a description of the changes you have made in the manuscript.

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[2] Two versions of the revised manuscript: one with either highlights or tracked changes denoting where the text has been changed; the other a clean version (uploaded as the manuscript file).

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Thank you again for your submission to our journal. We hope that our editorial process has been constructive so far, and we welcome your feedback at any time. Please don't hesitate to contact us if you have any questions or comments.

Sincerely,

Yvonne Su, Ph.D.

Guest Editor

PLOS Pathogens

Marco Vignuzzi

Section Editor

PLOS Pathogens

Kasturi Haldar

Editor-in-Chief

PLOS Pathogens

orcid.org/0000-0001-5065-158X

Michael Malim

Editor-in-Chief

PLOS Pathogens

orcid.org/0000-0002-7699-2064

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Reviewer Comments (if any, and for reference):

Reviewer's Responses to Questions

Part I - Summary

Please use this section to discuss strengths/weaknesses of study, novelty/significance, general execution and scholarship.

Reviewer #1: In this resubmission, the authors have made extensive textual edits throughout this manuscript, and have contributed additional information that was lacking in the original submission. These changes have improved the quality and utility of this study. However, there are still areas in the manuscript which warrant further improvement.

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Part II – Major Issues: Key Experiments Required for Acceptance

Please use this section to detail the key new experiments or modifications of existing experiments that should be absolutely required to validate study conclusions.

Generally, there should be no more than 3 such required experiments or major modifications for a "Major Revision" recommendation. If more than 3 experiments are necessary to validate the study conclusions, then you are encouraged to recommend "Reject".

Reviewer #1: Inclusion of a new Figure 1A is helpful to understand the magnitude of amino acid differences present between the two viruses under study, but is still lacking specificity. Considering the high number of nonsynonymous changes in the HA between the two viruses (including in HA1, which could impact receptor binding specificity), it would be beneficial if the authors provided a supplemental table to disclose exactly which amino acid changes are present in this protein between the two viruses. In PMID 21430049 (which shares authors with this study), several sites in the HA, including those linked with antigenic sites, were identified between H3N8 equine viruses over time; providing a list of amino acid differences in the HA for the two viruses under investigation here would thus be very helpful to the reader.

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Part III – Minor Issues: Editorial and Data Presentation Modifications

Please use this section for editorial suggestions as well as relatively minor modifications of existing data that would enhance clarity.

Reviewer #1: 1. Lines 52 and 135: authors state they are examining differences in “infection phenotype” but are employing replication-based assays in Figure 1B and 1D to assess this; wording should be changed to replication so not to mislead the reader, and to better match how the authors describe these investigations on line 168 (“virus growth kinetics and cell to cell spread”).

2. Lines 451-454: the authors state that the plasmids for EIV/63 are derived from reference 63, and the plasmids for EIV/2003 are derived from reference 64; however, it appears that reference 63 is incomplete (is this a dissertation? Book chapter?) so the reader cannot follow what the authors are conveying, and reference 64 only mentions plasmids from EIV/63, not EIV/2003. Please ensure both of these references are correct and accurately link to the information intended.

3. The authors state in their response to reviewer comments that the limit of detection for plaque assays was 10 PFU, but did not include this information in the methods section; please add this. In this vein, Figures 1B and 1D show mock-infected cells had titers of 0 PFU/ml which would be below the limit of detection for this assay, and should be adjusted accordingly.

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Reviewer #1: No

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Revision 1

Attachments
Attachment
Submitted filename: Rebuttal letter_submissionV2.docx
Decision Letter - Marco Vignuzzi, Editor

Dear Prof. Murcia,

We are pleased to inform you that your manuscript 'Long-term adaptation following influenza A virus host shifts results in increased within-host viral fitness due to higher replication rates, broader dissemination within the respiratory epithelium and reduced tissue damage' has been provisionally accepted for publication in PLOS Pathogens.

Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests.

Please note that your manuscript will not be scheduled for publication until you have made the required changes, so a swift response is appreciated.

IMPORTANT: The editorial review process is now complete. PLOS will only permit corrections to spelling, formatting or significant scientific errors from this point onwards. Requests for major changes, or any which affect the scientific understanding of your work, will cause delays to the publication date of your manuscript.

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Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Pathogens.

Best regards,

Marco Vignuzzi, Ph.D.

Section Editor

PLOS Pathogens

Marco Vignuzzi

Section Editor

PLOS Pathogens

Kasturi Haldar

Editor-in-Chief

PLOS Pathogens

orcid.org/0000-0001-5065-158X

Michael Malim

Editor-in-Chief

PLOS Pathogens

orcid.org/0000-0002-7699-2064

***********************************************************

Thank you for this revised version, all comments have been addressed.

Reviewer Comments (if any, and for reference):

Formally Accepted
Acceptance Letter - Marco Vignuzzi, Editor

Dear Prof. Murcia,

We are delighted to inform you that your manuscript, "Long-term adaptation following influenza A virus host shifts results in increased within-host viral fitness due to higher replication rates, broader dissemination within the respiratory epithelium and reduced tissue damage," has been formally accepted for publication in PLOS Pathogens.

We have now passed your article onto the PLOS Production Department who will complete the rest of the pre-publication process. All authors will receive a confirmation email upon publication.

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Thank you again for supporting open-access publishing; we are looking forward to publishing your work in PLOS Pathogens.

Best regards,

Kasturi Haldar

Editor-in-Chief

PLOS Pathogens

orcid.org/0000-0001-5065-158X

Michael Malim

Editor-in-Chief

PLOS Pathogens

orcid.org/0000-0002-7699-2064

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