Peer Review History

Original SubmissionJuly 29, 2019
Decision Letter - Cristian Apetrei, Editor

PONE-D-19-21147

Toll-like receptor 7-adapter complex modulates interferon-� production in HIV-stimulated plasmacytoid dendritic cells

PLOS ONE

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Cristian Apetrei, MD, PhD

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PLOS ONE

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Reviewers' comments:

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Comments to the Author

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Reviewer #1: Yes

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Reviewer #1: Yes

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Reviewer #1: Yes

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Reviewer #1: Yes

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5. Review Comments to the Author

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Reviewer #1: In the manuscript the authors investigate the mechanism responsible for a wide variation in the production of INF-a by plasmocytoid dendritic cells (pDCs) in HIV infection. They use four different cohorts: uninfected donors, subjects from the Amsterdam cohort study prior infection, elite controllers that maintain a plasma viral load below 50copies/ml in absence of ART, and progressor subjects. In the study, the authors suggest that the variation in the INF-a production is not due to viral entry efficiency or to the INF-a expression pathway mediated by TLR7/MyD88 complex interaction. Also, they did not observe correlation between the level of INF-a production before infection and disease progression.

The paper is well written and easy to read and understand.

Comments:

1. Table 1: Is the plasma viral load for the progressor subjects below 50 copies/ml?

2. For clarity, the authors should name the panels in the figures and refer to them when describing the results.

3. Figure legends should include more details about the experiments/results

4. Why did the authors use inactivated HIV particles to stimulate pDCs?

5. Did the authors try to stimulate pDC with different amounts of inactivated HIV particles or RNA41 to avoid saturation of CD4 binding or in the expression pathway or INF-a?

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Reviewer #1: No

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Revision 1

1. Table 1: Is the plasma viral load for the progressor subjects below 50 copies/ml?

We have now clarified that the progressor participants had a history of uncontrolled viremia (to distinguish them from LTNP/EC) but were stably suppressed to <50 copies/ml at the time of measurement in the Methods and legend to Table 1.

2. For clarity, the authors should name the panels in the figures and refer to them when describing the results.

The panels in figures with multiple graphs have been labeled and additional details were added to the results section where figures are referenced.

3. Figure legends should include more details about the experiments/results

The figure legends were revised to include a result in the title and methods in the descriptions.

4. Why did the authors use inactivated HIV particles to stimulate pDCs?

2-aldithriol-inactivated (AT-2) HIV particles have been compared to infectious particles in one study (Sabado et al., Plos One, 2019). They found that inactivated particles are slightly better for antigen presentation. Although the mechanism for this difference is unclear, we primarily used them because we with to avoid a perception of diminished pDC function possibly caused by HIV infection and their use is widespread in this field permitting direct comparisons with our results.

5. Did the authors try to stimulate pDC with different amounts of inactivated HIV particles or RNA41 to avoid saturation of CD4 binding or in the expression pathway or INF-a?

The amount of AT-2 inactivated HIV-1 particles (HIV-1ADA) was titrated in preliminary work (Tilton et al., ref 15). Those titrations indicated that amounts higher than 250 ng of AT-2 inactivated HIV-1 particles did not result in greater amounts of INF-a production. Saturation would be expected to cause less of an increase in IFN-a production for each increase in particle dose, lessening inter-patient variation. However, these variations occurred despite these high doses. Use of a high amount in the present paper permits us to explore the potential mechanism regarding these variations.

Attachments
Attachment
Submitted filename: Response to Reviewers.docx
Decision Letter - Cristian Apetrei, Editor

Toll-like receptor 7-adapter complex modulates interferon-� production in HIV-stimulated plasmacytoid dendritic cells

PONE-D-19-21147R1

Dear Dr. Connors,

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

Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.

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With kind regards,

Cristian Apetrei, MD, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Formally Accepted
Acceptance Letter - Cristian Apetrei, Editor

PONE-D-19-21147R1

Toll-like receptor 7-adapter complex modulates interferon-α production in HIV-stimulated plasmacytoid dendritic cells

Dear Dr. Connors:

I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

For any other questions or concerns, please email plosone@plos.org.

Thank you for submitting your work to PLOS ONE.

With kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Cristian Apetrei

Academic Editor

PLOS ONE

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