https://orcid.org/0000-0001-9753-3564
Peer Review History
| Original SubmissionJuly 1, 2022 |
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Dear Dr van Riel, Thank you very much for submitting your manuscript "Evolution of highly pathogenic H5N1 influenza A virus in the central nervous system of ferrets" for consideration at PLOS Pathogens. As with all papers reviewed by the journal, your manuscript was reviewed by members of the editorial board and by several independent reviewers. In light of the reviews (below this email), we would like to invite the resubmission of a significantly-revised version that takes into account the reviewers' comments. The concerns raised by Reviewer 2, in particular, should be carefully considered including how to address the concern that the CNS-associated virus mutations do not cause the same phenotype in ferrets. The biological relevance of the virus mutations must be addressed. We cannot make any decision about publication until we have seen the revised manuscript and your response to the reviewers' comments. Your revised manuscript is also likely to be sent to reviewers for further evaluation. When you are ready to resubmit, please upload the following: [1] A letter containing a detailed list of your responses to the review comments and a description of the changes you have made in the manuscript. Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out. [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). Important additional instructions are given below your reviewer comments. Please prepare and submit your revised manuscript within 60 days. If you anticipate any delay, please let us know the expected resubmission date by replying to this email. Please note that revised manuscripts received after the 60-day due date may require evaluation and peer review similar to newly submitted manuscripts. Thank you again for your submission. 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, Sabra L. Klein Associate Editor PLOS Pathogens Ana Fernandez-Sesma Section Editor PLOS Pathogens Kasturi Haldar Editor-in-Chief PLOS Pathogens orcid.org/0000-0001-5065-158X Michael Malim Editor-in-Chief PLOS Pathogens *********************** The concerns raised by Reviewer 2, in particular, should be carefully considered including how to address the concern that the CNS-associated virus mutations do not cause the same phenotype in ferrets. The biological relevance of the virus mutations must be addressed. 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: Siegers et al have performed detailed experiments to explore the mechanisms by which the HPAI H5N1 virus evolves in the mammalian CNS. The authors demonstrate that an HPAI H5N1 virus can enter the CNS via the olfactory nerve without a genetic bottleneck. And the authors conclude that viral dynamics within the CNS are conducive to positive selection, which gives the potential for improvement of viral replicative capacity and may lead to more severe disease. Reviewer #2: Professor van Riel and colleagues report findings from in vitro and in vivo studies that examined the contribution of specific amino acid residues of an H5N1 influenza A virus strain to CNS invasion and neurological disease. Cell culture studies revealed that the CNS-associated mutations enhanced the in vitro viral replication phenotype. Follow-up analysis with the ferret model of influenza and an H5N1 influenza virus strain harboring these putative CNS-associated mutations revealed an attenuated viral phenotype, including restricted tissue distribution. The results suggest the consequence of positive selection on viral phenotypes and potential evolution of influenza viruses. ********** 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: 1.Lines 104-111. Please explain why the change in the surface potential from negative to neutral in the apo form and from moderately negative to moderately positive charge in the promotor-bound form influence interactions with potential (host) binging factors? 2. Lines 133-137. Both the single substitution PB1-652T and the combined substitutions PB1-652T/177G with NP-119M can result in a significant increase of polymerase activity in A549 cells. However, the combination of PB1-652T with NP-119M maintained wild-type levels of polymerase activity. Please give some reasonable explanation for these phenotypes that seem contradictory. Reviewer #2: Genetic analysis of the viral population within the nasal cavity did not reveal a potential bottleneck or selection of virus with CNS-associated mutations. These results suggest the possibility that viral quasispecies contribute to the observed CNS invasive phenotype, neurological disease, and broad tissue distribution, which was lost by selection of a specific viral strain with the CNS-associated mutations. Another limitation of the study is that this phenotype was observed for one infected ferret. It is unclear how the host-specific response of this one animal contributed to the observed phenotype and if the selective forces are reproducible in shaping evolution of influenza viruses. ********** 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.It is better to specify which amino acids were site-directed mutated to generate the H5N1-CNS virus in Materials and methods or anywhere proper. 2.Line 125. Where are the large positively charged RNA-biding grove? Please highlight it in the supplementary figure 5. 3. Line 127. “different ‘human’ cell types” is suggested for more specific description. 4.Fig 5. Whether the difference of genetic diversity is significant statistically? Line 205. 5.Line 205. The study aimed to explore the CNS-associated mutations of an H5N1 HPAIV, did not involve reassortment events among different viruses, so “variant” may be appropriate than “genotypes”. 6.Lines 222, 223. Please provide more information to explain what the sentence “it is highly unlikely for common variants penetrated the CNS from the nasal turbinate” . 7.Line 278. what’s means of “stochastic fixation”？ 8. Statistical method in Fig. 2. Whether one-way ANOVA should be used instead of two-way ANOVA? Reviewer #2: not-applicable ********** PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes: Honglei Sun Reviewer #2: No Figure Files: While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org. Data Requirements: Please note that, as a condition of publication, PLOS' data policy requires that you make available all data used to draw the conclusions outlined in your manuscript. Data must be deposited in an appropriate repository, included within the body of the manuscript, or uploaded as supporting information. This includes all numerical values that were used to generate graphs, histograms etc.. For an example see here on PLOS Biology: http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001908#s5. Reproducibility: To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols |
| Revision 1 |
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Dear Dr van Riel, We are pleased to inform you that your manuscript 'Evolution of highly pathogenic H5N1 influenza A virus in the central nervous system of ferrets' 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. Should you, your institution's press office or the journal office choose to press release your paper, you will automatically be opted out of early publication. We ask that you notify us now if you or your institution is planning to press release the article. All press must be co-ordinated with PLOS. Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Pathogens. Best regards, Sabra L. Klein Academic Editor PLOS Pathogens Ana Fernandez-Sesma Section Editor PLOS Pathogens Kasturi Haldar Editor-in-Chief PLOS Pathogens orcid.org/0000-0001-5065-158X Michael Malim Editor-in-Chief PLOS Pathogens *********************************************************** 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: The manuscript modification meets the requirement. Reviewer #2: This in vivo study examined the replication phenotype and tissue distribution of H5N1 highly pathogenic avian influenza virus in the ferret model of influenza. The authors note that the findings are limited to one animal but the data indicate the impact of genetic evolution for virus replication and viral pathogenesis. Overall, the authors deserve high marks for execution and scholarship. ********** 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: No Reviewer #2: Not applicable. ********** 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: No Reviewer #2: Not applicable. ********** PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No |
| Formally Accepted |
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Dear Dr van Riel, We are delighted to inform you that your manuscript, "Evolution of highly pathogenic H5N1 influenza A virus in the central nervous system of ferrets," 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. The corresponding author will soon be receiving a typeset proof for review, to ensure errors have not been introduced during production. Please review the PDF proof of your manuscript carefully, as this is the last chance to correct any scientific or type-setting errors. Please note that major changes, or those which affect the scientific understanding of the work, will likely cause delays to the publication date of your manuscript. Note: Proofs for Front Matter articles (Pearls, Reviews, Opinions, etc...) are generated on a different schedule and may not be made available as quickly. Soon after your final files are uploaded, the early version of your manuscript, if you opted to have an early version of your article, will be published online. The date of the early version will be your article's publication date. The final article will be published to the same URL, and all versions of the paper will be accessible to readers. 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 |
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