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Review
Peer-Review Record

Impact of Natural Occurring ERAP1 Single Nucleotide Polymorphisms within miRNA-Binding Sites on HCMV Infection

Int. J. Mol. Sci. 2020, 21(16), 5861; https://doi.org/10.3390/ijms21165861
by Ombretta Melaiu *,†, Silvia D’Amico †, Patrizia Tempora, Valeria Lucarini and Doriana Fruci *
Reviewer 1: Anonymous
Reviewer 2: Anonymous
Reviewer 3: Anonymous
Int. J. Mol. Sci. 2020, 21(16), 5861; https://doi.org/10.3390/ijms21165861
Submission received: 22 July 2020 / Revised: 10 August 2020 / Accepted: 12 August 2020 / Published: 15 August 2020

Round 1

Reviewer 1 Report

The review is well written and structured. The topic is well developed. Furthermore, I believe that this review can help to better understand the role of erap1 in HCMV infection. However, I strongly suggest to add  a paragraph on miRNAs and ERAP1 with direct / indirect effect to get a general overview of how many miRNAs can influence the expression of erap.  

Only one mistake I noticed:

line103: from which should be correct in form which

Author Response

The review is well written and structured. The topic is well developed. Furthermore, I believe that this review can help to better understand the role of erap1 in HCMV infection. However, I strongly suggest to add  a paragraph on miRNAs and ERAP1 with direct / indirect effect to get a general overview of how many miRNAs can influence the expression of erap.  

Only one mistake I noticed:

line103: from which should be correct in form which

We thank the Reviewer for the comment. As requested, a general overview of miRNAs that affect the expression of ERAP1 has been included (page 4, line 160) and the form at line 103 (pag 3) has been corrected.

Reviewer 2 Report

This is a well written review that focuses on the role of HCMV miRNAs in immune evasion.  The authors have developed the interesting hypothesis that HCMV miRNAs target ERAP1, and that naturally occurring polymorphisms in this gene affect the ability of HCMV miRNAs to modulate expression of the protein, and thus, presentation of antigens to CD8+ T cells.

The authors provide a succinct and informative review of HCMV miRNAs, the biological function of ERAP1, and the potential role of ERAP1 polymorphisms in human disease.  They have developed a bioinformatics pipeline to identify SNPs in the ERAP1 3’UTR that may be targeted by HCMV miRNAs.  The results of these analyses are well presented in the tables and figures, and they have convincingly narrowed the potential targets down to a few candidates that could be tested experimentally.

There are a number of minor grammatical errors.  Some examples:

Line 11: causes, not cause

Line 12: it coexists

Line 14: suggest “expression of viral microRNAs is one of the most intriguing”.

Line 16: highly

Line 17: should be “incomplete picture”?

Line 90: should be “largest” rather than “larger”?

Line 95: rephrase.

Author Response

There are a number of minor grammatical errors.  Some examples:

Line 11: causes, not cause

Line 12: it coexists

Line 14: suggest “expression of viral microRNAs is one of the most intriguing”.

Line 16: highly

Line 17: should be “incomplete picture”?

Line 90: should be “largest” rather than “larger”?

Line 95: rephrase.

We would like to thank the Reviewer for the comments and observation. All the indicated sentences were rephrased (page 1, lines 11, 12, 14, 16 and 17; page 3 lines 90 and 95) and the entire manuscript carefully revised for English editing.

Reviewer 3 Report

This is a very nicely written review on the impact of SNP variation within a key target of human cytomegalovirus encoded microRNAs specifically within the ERAP1 gene which functions in immune evasion.  It is well written, very clear and an important study to the field.

Author Response

We would like to thank the Reviewer for the comments.

Round 2

Reviewer 1 Report

the authors reviewed the work correctly

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