https://orcid.org/0000-0002-6970-6728
Peer Review History
| Original SubmissionJuly 21, 2023 |
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Dear Professor Rinaldo, Thank you very much for submitting your manuscript "Modelling BK Polyomavirus dissemination and cytopathology using polarized human renal tubule epithelial cells" 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. The reviewers appreciated the attention to an important topic. Based on the reviews, we are likely to accept this manuscript for publication, providing that you modify the manuscript according to the review recommendations. 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. When you are ready to resubmit, please upload the following: [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. 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. 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, Walter J. Atwood Academic Editor PLOS Pathogens Patrick Hearing 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: BKPyV primaryly infects renal tubular cells and has the potential to destroy the kidney in immunosuppressed individuals; this infection is particularly detrimental in renal transplant recipients. It is currently assumed that intrarenal dissemination of the virus occurs by continuity in renal tubules, however, a detail understanding of this process is not known. In this study the BKPyV infection is evaluated in a polarized renal proximal tubule epithelial cell line that has the potential to most closely resemble the infectious process in renal tubules. The study is novel and has experimental/methodological value. Furthermore, conclusions from this study help better understand the lag between the earlier stages of infection and the onset of clinical manifestations, Reviewer #2: In this manuscript (PPATHOGENS-D-23-01211), Lorentzen et al describe a new cultured cell model system to study infection by the pathogenic human polyomavirus, BKPyV. BKV infection is widespread in the population and causes severe disease in immunosuppressed individuals, such as renal transplant recipients and patients undergoing bone marrow or stem cell transplants. BKV normally replicates in polarized renal tubule epithelial cells, but in vitro studies are performed in monolayer cell cultures. A few years ago, the Imperiale lab described BKV replication in cultured non-polarized renal proximal tubule epithelial cells (RPTECs). Here, the authors establish polarized cultures of RPTECs on permeable inserts, show BKV replication and cytopathic effects in infected cells, and that the virus preferentially infects and is released from the apical surface (as is the case for the closely related primate polyomavirus, SV40, which also replicates preferentially in kidney), until very late in infection. Virus is also contained in extruded cells with maintenance of epithelial integrity. The work appears competently done and this is likely to be a valuable model system to study this virus. However, the current work is largely descriptive, and they have not yet used the system to provide new mechanistic insights into BKV replication or pathogenesis. ********** 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: None. Reviewer #2: 1. This manuscript would be greatly strengthened if they use their system to address unanswered questions regarding BKV replication or pathogenesis. 2. Their model for how BKV spreads in vivo is intriguing and consistent with their in vitro studies, but not directly addressed in the experiments. ********** 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: - In the materials and methods, immunofluorescence staining and microscopy section, a list of antibodies is presented without further clarification. Some of these antibodies are never mentioned in the text and are only mentioned in the figure legends. Since evaluation of the polarized renal tubular cell line is relatively novel, it would be useful if the authors could briefly explain the purpose of the stains. For example, separate stains for characterization of the viral infection from the stains done to characterize the tubular cell itself (ZO-1, tubulin, etc). - There is a typo in the last line of page 16 (pylon should be pelvis) Reviewer #2: They should define “decoy cells”. The use of the word “sank” on line 210 is unclear. ********** 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 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: 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 References: Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. |
| Revision 1 |
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Dear Professor Rinaldo, We are pleased to inform you that your manuscript 'Modelling BK Polyomavirus dissemination and cytopathology using polarized human renal tubule epithelial cells' 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, Walter J. Atwood Academic Editor PLOS Pathogens Patrick Hearing 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): |
| Formally Accepted |
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Dear Professor Rinaldo, We are delighted to inform you that your manuscript, " Modelling BK Polyomavirus dissemination and cytopathology using polarized human renal tubule epithelial cells ," 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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