A Perfect Storm: The Convergence of Aging, Human Immunodeficiency Virus Infection, and Inflammasome Dysregulation
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThe aim of this manuscript is to review the relationship between HIV infection and inflammation, specifically focusing on the effect of HIV infection on the inflammasome. This is a very interesting review. Several comments are provided below:
- The general epidemiology of patients with HIV, including factors such as age, race, gender, and nationality, should be reviewed to provide a comprehensive understanding of the population under study.
- The financial status and living conditions of patients with HIV should be mentioned, as both factors can significantly impact the aging process and contribute to inflammation.
- Other medical histories of patients with HIV, such as IVDU, CAD, HTN, smoking, and alcohol use, should be discussed. These medical histories may also play a role in the formation of the inflammasome and should be considered in the context of HIV-related inflammation.
Author Response
Reviewer 1 :
Comment from Reviewer 1: The aim of this manuscript is to review the relationship between HIV infection and inflammation, specifically focusing on the effect of HIV infection on the inflammasome. This is a very interesting review.
Author response: We appreciate the reviewer’s kind and helpful comments. Below are the answers to specific comments.
- The general epidemiology of patients with HIV, including factors such as age, race, gender, and nationality, should be reviewed to provide a comprehensive understanding of the population under study.
Author Response: As suggested by the reviewer, we have now included the general epidemiology of patients with HIV in the introduction.
- The financial status and living conditions of patients with HIV should be mentioned, as both factors can significantly impact the aging process and contribute to inflammation.
Author Response: We have now included the financial status and living conditions of patients with HIV in the introduction.
3. Other medical histories of patients with HIV, such as IVDU, CAD, HTN, smoking, and alcohol use, should be discussed. These medical histories may also play a role in the formation of the inflammasome and should be considered in the context of HIV-related inflammation.
Author response: As suggested by the reviewer, we have also discussed the impact of substance abuse in the introduction section.
Reviewer 2 Report
Comments and Suggestions for Authors
A Perfect Storm: The Convergence of Aging, HIV Infection, and Inflammasome Dysregulation
The present review outlines the inflammatory processes triggered by HIV-1 infection and aging, focusing on the inflammasomes and exploring current research on inflammasomes and strategies to mitigate inflammation. This review further suggests that future research on inflammasome signaling presents a unique opportunity to develop targeted interventions and innovative therapeutic modalities for combating HIV and aging-associated inflammatory processes. This review article is well-formulated and nicely written. Following are the specific comments to strengthen the manuscript further,
1. In Figure 1, the opportunistic co-infection with other viruses and bacteria may be added.
2. Are inflammasome inhibitors useful therapeutics to prevent inflammation and inflammaging? If yes, can these drugs be co-administered with ART? Any explanation of this could help in the future therapeutic treatment of inflammaging.
Author Response
Comment from Reviewer 2: The present review outlines the inflammatory processes triggered by HIV-1 infection and aging, focusing on the inflammasomes and exploring current research on inflammasomes and strategies to mitigate inflammation. This review further suggests that future research on inflammasome signaling presents a unique opportunity to develop targeted interventions and innovative therapeutic modalities for combating HIV and aging-associated inflammatory processes. This review article is well-formulated and nicely written.
Author response: We are thankful for the reviewer’s comments. Below are the answers to specific comments.
- In Figure 1, the opportunistic co-infection with other viruses and bacteria may be added.
Author response: As reviewer pointed out, opportunistic co-infection with other pathogens also had major impact inflammasome activation in elderly and people with HIV. However we did not include that the Figure 1 because our review is focused on the specific topic of the role of inflammasome at the intersection of HIV and aging. The role of other opportunistic infections, though likely, is beyond the scope of this review.
- Are inflammasome inhibitors useful therapeutics to prevent inflammation and inflammaging? If yes, can these drugs be co-administered with ART? Any explanation of this could help in the future therapeutic treatment of inflammaging.
Author response: We agree with the reviewer’s comment. Indeed, we have discussed inflammasome inhibitors as useful therapeutics in controlling the inflammation in the “Inflammasomes as Therapeutic Targets” section. However, more studies are needed to optimize dose and learn about potential drug interactions and side effects when they are co-administered with ART. We have now added this to our discussion in “Inflammasomes as Therapeutic Targets” section.
Reviewer 3 Report
Comments and Suggestions for AuthorsThis review also explores current research regarding inflammasomes and potential strategies for targeting inflammasomes to mitigate inflammation.
It may help provide information about inflammasomes. However, the following needs to be supplemented:
Please provide original language regarding HIV and PWH.
In the introduction, please add the results of a review of previous research to suggest the need for research. Please describe the need for research in more detail based on the added review results.
Additionally, please explain the background of the main detailed sub-titles in the introduction.
Other than that, it is well organized overall. Thank you for your effort.
Author Response
Comment from Reviewer 3: This review also explores current research regarding inflammasomes and potential strategies for targeting inflammasomes to mitigate inflammation. It may help provide information about inflammasomes. However, the following needs to be supplemented:
- Please provide original language regarding HIV and PWH.
Author response: We thank the reviewer for this suggestion. We have included the expansions for HIV and PWH.
- In the introduction, please add the results of a review of previous research to suggest the need for research. Please describe the need for research in more detail based on the added review results.
Author response: Thank you for your feedback. The reviewer is absolutely right that previous reviews have addressed the need for research on inflammasomes in HIV and aging individually. However, the unique focus of our review is the intersection of these two factors. We aim to highlight the critical gap in knowledge regarding the specific role of inflammasome pathways in elderly individuals living with HIV and people undergoing accelerated ageing process by HIV infection. By synthesizing existing research on inflammasomes in both aging and HIV, and then identifying the areas where this knowledge base is lacking in the context of co-occurring HIV and aging, we underscore the urgent need for targeted research in this specific demographic. We will incorporate this clarification into the introduction to better emphasize the novel perspective of our review.
- Additionally, please explain the background of the main detailed sub-titles in the introduction.
Author response: Thank you for this suggestion. We have already discussed inflammation in HIV and aging. Now we included inflammasomes in the introduction section.
Other than that, it is well organized overall. Thank you for your effort.
Author response: We are thankful for the reviewer’s kind comments.
