Peer Review History
Original SubmissionFebruary 26, 2021 |
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Dear Dr. Ros, Thank you very much for submitting your manuscript "Human parvovirus B19 interacts with globoside under acidic conditions as an essential step in endocytic trafficking" 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, Patrick Hearing Associate Editor PLOS Pathogens Erik Flemington 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 “Parvo B19 interacts with globoside under acidic conditions to facilitate endocytic trafficking” by Bieri, Leisi, Bircher and Ros is aa comprehensive and elegant study that redefines the role of Gb4 in infection of cells by B19. Gb4 was previously thought to be the principle cell surface receptor for B19 based on virus binding to Gb4 and the fact that Gb4 knockouts are resistant to infection. The broad cellular distribution of Gb4 however is counter to the restricted tropism of the virus. The authors show that rather than playing a role in initial binding to cells that Gb4 plays a fundamental role downstream of initial entry to facilitate endocytic trafficking of the viral particle and its genome to the nucleus to initiate infection. Another cell surface molecule identified only as VPu-Receptor is the major cell surface receptor for the virus and its expression is highly restricted to erythroid progenitor cells (EPC). This paper focuses on the role of Gb4, confirms its interaction with B19 capsids, and defines the cellular requirements that dictate those interactions. In summary this is an elegant and comprehensive paper, the data are clean and convincing, and certainly support their major conclusions. Reviewer #2: Bieri and colleagues provide compelling evidence that a specific sphingoglycoprotein, designated Gb4, is a host factor for parvovirus B19 entry into erythroid progenitor cells. Although the principal attachment receptor for this virus has yet to be identified, it appears that cell tropism is largely determined by recognition of Gb4 that presumably interacts with the VP2 capsid protein. The authors show that this interaction does not occur at neutral pH, thereby explaining how the broad distribution of Gb4 does not result in infection of non-productive host cells. Rather the Gb4-B19 virus interaction occurs at a reduced pH, similar to that found in endocytic vesicles. Abrogation of Gb4 in cells deficient of this molecule results in efficient virus attachment and internalization, however the virus fails to progress and remains trapped in vesicles. The results are quite clear as presented and add a new dimension to our understanding of how multiple host cell molecules facilitate virus entry. I have only a few suggestions for the authors to consider in order to clarify a few sections of the paper. 1. The authors could bolster the Discussion a bit with regards to the identity of the unknown attachment receptor. For example, do they know the relative binding affinity for the putative receptor vs that for Gb4? 2. Figure 5C. I cannot find a description of the results of this experiment in the text. I think it may have been omitted accidentally by the authors. 3. Why doesn’t the interaction of the virus with Gb4 at low pH result in capsid protein production given that NS1 mRNA is detected at a normal level as shown in Figure 6D. 4. Line 248. I suggest a modification of the title as follows: The early endosomal compartment provides optimal conditions for Gb4 interaction. 5. The Material and Methods are lacking in sufficient detail in a few places: Line 469. Please specify the source of the B19 used in this study (is this a clinical specimen or one purchased, etc)? Line 513. Please give more details of the confocal microscopy. Line 535. How was viral NS1 mRNA quantified and what primers may have been used? Reviewer #3: The manuscript by Bieri et al., describes, in a comprehensive set of experiments, the role of globoside in the life cycle of human parvovirus B19. This laboratory has made seminal contributions in the past relating to B19 biology, and the current studies are a fine example of their thoughtful rationale, careful planning of experiments, and lucid presentation of the data. Overall, this is a well-written manuscript in which the quality of the data presented is good, and the conclusions drawn are generally supported by the data shown. ********** 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: (No Response) Reviewer #3: None. ********** 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: The abstract on the manuscript submission form differs slightly from the abstract in the manuscript and the former has some confusing typos such as: 1st sentence: The glycosphingolipid (GSL) globoside (Gb4) this study, we applied artificial viral particles, genetically modified cells, and specific competitors to address the interplay between the virus and the GSL. Figure 1A and S2 don’t seem to fit with the results: “The expression of VP1uR in cells was sufficient to trigger virus attachment and uptake, however, in the absence of Gb4, the intracellular capsids failed to initiate the infection (Figs 1A and S2)”. These figures are not showing failure to infect…1A is detection of receptor in GB4 KOs and S2 is showing cell cycle arrest. Please clarify. Reviewer #2: Include a description of the studies shown in FIgure 5C. Reviewer #3: The authors may wish to address the following points, which may be helpful to the reader: 1. While it is known that exposure to low pH alone is sufficient for the structural change observed in the adenovirus capsid, previous studies with AAV have suggested that exposure to low pH is necessary but not sufficient (J. Virol., 75: 4080-4090, 2001). Since B19 would also be expected to encounter similar intracellular milieu, in addition to pH changes, which may not directly mimic the in vitro experimental conditions. 2. Parvovirus B19 binding to RBCs in vitro may also not truly mimic a natural infection in vivo. Weigel-Kelley et al, have proposed that human parvovirus B19 binds to mature erythrocytes, which facilitate trafficking of the virus to the bone marrow where the target cells reside (Blood, 102: 3927-3933, 2003). This reference should be cited. ********** 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 Reviewer #3: 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.. 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Revision 1 |
Dear Dr. Ros, We are pleased to inform you that your manuscript 'Human parvovirus B19 interacts with globoside under acidic conditions as an essential step in endocytic trafficking' 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, Patrick Hearing Associate Editor PLOS Pathogens Erik Flemington 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 |
Dear Dr. Ros, We are delighted to inform you that your manuscript, "Human parvovirus B19 interacts with globoside under acidic conditions as an essential step in endocytic trafficking," 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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