PONE-D-20-30396

Analysis of lung transcriptome in calves infected with Bovine Respiratory Syncytial Virus and treated with antiviral and/or cyclooxygenase inhibitor

PLOS ONE

Dear Dr. Gershwin,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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 As cited by Reviewer-2, the authors should include additional data to support their claim on the genome-wide transcriptome analysis. It is important to relate the disease pathology (lung lesions) or no pathology (no lesions) to corresponding transcriptome profile. This is needed to understand the relevance of the networks/pathways/genes that were reported to be differentially regulated in this article. In addition, as noted by Reviewer-1, the authors should re-organize the write-up to eliminate repetition of their results in the discussion section, and instead, highlighting what are the unique characteristics of their study, compared to published literature. 

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Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: I Don't Know

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: In the present study, the authors have presented lung transcriptomics of bovine lung upon BRSV infection. They further analyzed the effect of antiviral treatment regimen. In my opinion, it is a nice piece of work. However, I found redundant information have been provided at places. The discussion section can be presented precisely by removing the details of their findings, which have already been discussed in results section. Also, they should give precise information about any gene or physiological pathway while discussing.

Reviewer #2: Authors carried out differential gene expression analysis in Bovine Respiratory Syncytial virus (BRSV) infected lung tissues (LL vs LN) and shown that combined treatment with FPI and Ibuprofen, made the most difference in gene expression patterns in comparison with especially in pathways related to the innate and adaptive immune response in both LL and LN. Authors suggest that FPI in combination with ibuprofen would provide the best therapeutic intervention against BRSV infection. The study result is very interesting with future perspective but lack a lot of basic information. The present study has to address following questions.

Major comments:

Author investigated differential gene expression and pathway analysis between lung lesion (LL) and No lung lesion (LL) of different treatment groups. However, to understand the real time effect of your treatment, pathological and histo-pathological data must be included. Authors did not provide viral load in the lung as well as nasal swab in different group. Quantification of viral load will help to better interpret the results from gene expression and pathway analysis regarding to their phenotypical effect such as progression of disease.

Authors should provide pathological score to better understand how the treatment contributed to the resolution of disease/pathogenesis.

There is no histopathological data were provided, which help to determine clinical status of disease and also to understand the beneficial effect of treatment.

Authors analyzed differentially expressed gene and differentially regulated pathways between LL vs LN among treatment groups. It is interested to study the gene expression when the data analyzed between LL vs LL and LN vs LN among the treatment groups. Did authors carry out this analysis?

It will be better to estimate the production of PGE2, thromboxane and other pro-inflammatory cytokine/chemokine level to study the efficiency of treatment for control viral load as well as inflammation.

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Reviewer #1: No

Reviewer #2: No

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Analysis of lung transcriptome in calves infected with Bovine Respiratory Syncytial Virus and treated with antiviral and/or cyclooxygenase inhibitor

PONE-D-20-30396R1

Dear Dr. Gershwin,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Selvakumar Subbian, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: I Don't Know

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: (No Response)

Reviewer #2: Authors tried to address all the comments and revised the manuscript. However, authors mentioned that some of the data asked by the reviewer will be published separate paper.

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7. 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