This review and perspective piece establish multiple important questions in the basic ecology and evolution of viruses. It is a timely piece that well discusses multiple areas of promising research and is timely given the increase of virome work. I see this being an important manuscript to guide future research and an excellent manuscript to hand new graduate students. The abstract was clear and interesting. The area that I feel needs major improvement is the setup and structure of the main ideas in the introduction and perspectives. For example, the introduction hits at multiple complex ideas without clearly developing most of them or well preparing the reader for the main text. The perspective fails to pull everything together and instead ends with essentially a new idea. The main content of the manuscript is well thought out, complete, and easy to follow. Figures 1 and 2 are good illustrations and helps to support the manuscript main text, however, the “box” which is part of what makes this review original is disconnected from the text and would benefit by being better used in the main text. For example, the authors could expand upon and suggest these tangible applications for researchers directly in the main text and reshape the content for each factor they decided to talk about. It could be interesting to have a more concise message for each driver presented: what we know, what are the main outcomes, what challenges, how to face the challenges for viral communities, and research advice.

I provide some specific examples below to help expand upon the above comments and highlight a few other areas that I think could be clarified or improved upon.

There is an issue with the numeration within the review. The authors present the “ecological drivers of virome composition” in section “3” (line 196) and continue with “abiotic associations with virome diversity and abundance” in section “3.1” (L214) to skip directly to “Seasonal variations in viromes” in section “4.1.2” (L245) before resuming to section “3.2” “host biotic factors that shape virome composition” (L263).

L30: I suggest “This number is expected to increase dramatically”.

Line 57: The idea that these biases can lead to dogmas is confusing from the examples. For example, many zoonotic diseases linked to bats are after well establishing bats as reservoirs. I agree with the general idea being made here but do not think it is clear. An example the better establishes how the data on certain species leads to biased dogmas would benefit the section. To be clear myself, I mean to walk through if you have a new zoonotic virus and you search existing data and it most closely matches a bat virus you assume bats as a reservoir when really there is a more closely related virus in a sloth we have never sampled. Clearly differentiating your intentions from something like Nipah virus that is well established.

Line 63-79: The paragraph illustrates the major area of revision needed for the manuscript. The introduction hits on many different important ideas but fails to cohesively setup the focus of the paper. There is so much to potentially discuss, given the complex factors shaping viromes and the many meaningful things we can learn from them. This of course makes it very challenging to concisely set up the paper but also highlights the importance of doing so.
For example, it is unclear if this paragraph is about:
1. The unique challenges in studying viromes
2. The importance of determining barriers to cross-species virus transmission
3. Factors driving viral diversification and spread
4. Factors that structure viromes
5. What we can learn from these viromes – for example about disease emergence

By better establishing the flow and providing evidence to support the ideas a reader could better understand the goals of this manuscript. This paragraph can easily become three and the previous paragraph can be shortened.

L70 “a whole ecosystem” instead of “an whole ecosystem”.

Line 79: Distinction between invertebrate and vertebrate host viromes is not evidence for viruses being “Preferentially shared between closely related hosts”. Going from phylum level to “closely related” is a major leap.

Line 181-182: Please provide more detail on the bumblebee study to better support this argument. What is meant by “terms accounting for”?

Line 450: The paragraph summarizing the potential link to mitigation efforts brings in a relatively major idea at the end. This could be further expanded on and linked to the central ideas of the rest of the manuscript more. For example, are there mitigation actions that can be linked to understanding virome drivers linked to seasonality, phylogenetic relatedness, abiotic factors, etc?

In general, the final section could better integrate the ideas in the main text. I also see potential to call back to the Box as a path forward.

The revision was well done and clarified all points of confusion. The edits to the introduction and conclusions tied together the concepts and improved the overall messaging of the paper.