Viral Co-Infections and Antiviral Immunity in Honey Bees

Round 1

Reviewer 1 Report

The authors summarized current knowledge on honey bee antiviral immunity before reviewing the interactions between specific pathogenic viruses and their hosts. Finally, they draw hypotheses from the current literature and suggest future research directions. - The review is well-written, comprehensive, and well-organized. It was a pleasure to read. Its publication is thus very much valued. - I have a few suggestions and edits as follows: 1- Page 1, lines 21, 22: the authors should cite these relevant studies, respectively (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396518/; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9146872/). 2- Page 2, lines 78-79: Please provide appropriate references. 3- Page 5: section 2.4: melanization, It might be interesting to provide an overview of cellular immunity while also including melanization. 4- Page 6: line 230: Please provide appropriate references (ex, https://pubmed.ncbi.nlm.nih.gov/33653721/). 5- Page 8: section 3.1: I miss one or two sentences about other DWV variants like DWV-D, a distinct master strain of deformed wing virus linked to honeybee mortality in 1970's Egypt. 6- Page 8, line 319: what do you mean by secondary countries?? 7- Page 8, line 325: Al Naggar & Paxton also found DWV-B is more virulent than DWV-A: https://ami-journals.onlinelibrary.wiley.com/doi/10.1111/1751-7915.13673 8- Page 9, lines 359-361: what was the conclusion of this study? 9- Page 11, Perspectives section: A shift in the mode of transmission of honey bee viruses from fecal/food-oral (direct horizontal) to vector-mediated (indirect horizontal) might pose a future threat to bees and Apiculture. For example, An increase in virulence following a change in transmission route has been documented in an isopod and its endosymbiont Wolbachia (https://doi.org/10.1098/rspb.2017.1076), as well as in honey bees and their viruses: black queen cell virus (BQCV) and sacbrood virus (SBV) (https://doi.org/10.3390/v12050535., https://doi.org/10.1098/rspb.2018.2452). I would recommend the authors add one more paragraph to discuss that.

 

Comments for author File: Comments.pdf

Author Response

Dear reviewer,

Thank you for taking the time to read and comment our review. Your kind words have been appreciated, and your constructive suggestions truly helped improving our manuscript. In the following lines you will find the modifications that followed your suggestions, or elements of discussion as to why we kept some lines unchanged.

1 - L22-23 : Added suggested reference (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396518/)
     L27-28 : Added “as well as honey bee immune dynamics when facing them” along with the following suggested reference (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9146872/)

2 - L84 : Added references originally cited later in the manuscript (L128; L157; L185; L191)

3 - L174 : Thank you for your suggestion about broadening our chapter to all cellular immunity mechanisms while still including the melanisation response. This possibility has indeed been discussed prior to submission. However with this review, our aim is not to review all honey bee immune mechanisms, but those relevant to antiviral immunity. We therefore decided to narrow the scope of this chapter on melanisation and haemocytes, which are the cellular immunity mechanism targeting viruses.

4 - L241 : Added suggested reference already cited L224 (https://pubmed.ncbi.nlm.nih.gov/33653721/)

5 - L329-331 : Added a sentence about other DWV variants (DWV-C and DWV-D) and why we decided to focus on DWV-A and DWV-B : “Although other master variants have been described (DWV-C [179], DWV-D [180]), their respectively rare detection and disappearance incited research efforts to focus on the two most commonly detected master variants : DWV-A and DWV-B.”.

6 - L332 : By “secondary countries” we meant countries in which varroa was not previously present but has been newly introduced. Due to possible confusion, we replaced “The introduction of the mite in secondary countries first led to […]“ by “In previously spared countries, the introduction of the mite first led to […]”.

7 - L338 : Added suggested reference (https://ami-journals.onlinelibrary.wiley.com/doi/10.1111/1751-7915.13673)

8 - L378-379 : Added “and showed differential patterns of immune activation and inhibition that suggest potential interactions between the two viruses.” to the sentence as to emphasize the conclusions of the study, which are also detailed later in the chapter.

9 - L472-480 : Added the following paragraph to discuss the phenotypic changes associated with a shift in transmission routes : “[Different administration routes may trigger different immune and viral dynamics.] Indeed, changes in rates of replication and virulence has been found for BQCV [9,221] and SBV [9] between cases of oral inoculations and direct injections. In an other arthropod (Armadillidium vulgare), an common endosymbiont (Wolbachia) has been shown to become pathogenic when a shift from vertical to horizontal transmission occurs [222]. In all these cases, the change in transmission route made the microbe more virulent and increased its replication. As discussed in Section 3.1., a similar pattern has been observed when DWV became vectored by varroa, with differential immune gene expression between orally inoculated and varroa-mediated inoculated bees [79].”

Thank you again for reviewing our manuscript, in hope that you will be pleased with the new version.
Sincerely,
The authors

Reviewer 2 Report

This well-written review summarizes current knowledge of honey bee antiviral defenses and their interaction between virus complexes. The review provided a brief description of honey bee (insect) antiviral pathways and further focused on interactions between most common pathogenic virus (such as DWV-A and DWV-B, SBV,  CBPV, IAPV). 

Honey bees are among the insect species with the best studied viruses and virus-host interactions, therefore I feel that this review (which cited 224 paper published mostly in the last two decades) will be well-received by bee researchers and virology community in general. 

 

Minor suggestions: 

L 18. Abstract/ Key words /

Include Latin scientific name of the honey bee species described in this review (Apis mellifera, Apis cerana)

 

L. 29. Described -> detected 

Although this review focuses on honey bee, I feel that it is worth to cite couple of good reviews on antiviral defenses in insects in general: 

 

L 121-148(insect RNAi defenses): 

Schuster S, Miesen P, van Rij RP. Antiviral RNAi in Insects and Mammals: Parallels and Differences. Viruses. 2019; 11(5):448. https://doi.org/10.3390/v11050448

 

L. 150-152. (non-RNAi mediated  responses in insects): 

SH Merkling, RP van Rij. 2013 Beyond RNAi: antiviral defense strategies in Drosophila and mosquito.  Journal of Insect Physiology. 59: 159-170. https://doi.org/10.1016/j.jinsphys.2012.07.004

 

 

 

Author Response

Dear reviewer,

Thank you for taking the time to read and comment our review. Your kind words have been appreciated, and your constructive suggestions truly helped improving our manuscript. In the following lines you will find the modifications that followed your suggestions.

L18 : Apis mellifera and Apis cerana were added as keywords as suggested.

L31 : “described” has been changed to “detected”.

L84-86 : Added the sentence “Regarding physiological immune responses in insects, extensive work has been done in drosophila [49] and mosquito [50] models, facilitating more recent inquiries in honey bee immunity.” as to emphasize the importance of other insect models in the study of antiviral immunity.

L142 : Added suggested reference (https://doi.org/10.3390/v11050448)

L158 : Added suggested reference (https://doi.org/10.1016/j.jinsphys.2012.07.004)

Thank you again for reviewing our manuscript, in hope that you will be pleased with the new version.
Sincerely,
The authors