– Prof. Michael Betts
HIV persistence remains a central barrier to achieving durable viral remission, yet the immunological mechanisms that sustain infected cells within tissues continue to challenge the field. In this Q&A, Prof. Michael R Betts (Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA) discusses how decades of work in HIV immunology have shaped current understanding of CD8 T-cell function, tissue-based immunoregulation and the cellular features of the HIV reservoir, presented at the Centre of Excellence for Spatial Multi-Omics Research in Africa (CESORA) 2025 Symposium.
Drawing on emerging single-cell and spatial multi-omics approaches, he reflects on the evolving landscape of HIV reservoir biology, the parallels highlighted across HIV, TB and HPV at the CESORA Symposium, and the importance of cross-disciplinary learning in advancing HIV cure research.
My lab has studied immunological mechanisms of protection and control in HIV infection since 2005. Over this time, we have developed a model wherein the inability of the CD8 T-cell response to eliminate persistent HIV-infected cells in lymph nodes and other tissues is associated with poor CD8 cytotoxic responses and immunoregulation. Through these studies we further appreciated the need to understand the nature of the target for HIV-specific CD8 T cells – HIV-infected CD4 T cells in tissues.
Building upon our knowledge of CD4 T-cell heterogeneity, we recognised the need for single-cell methodologies and began to develop strategies to use single-cell omics approaches to identify infected cells in lymph nodes.
Currently, we have not yet embarked upon spatial multi-omics in my laboratory. In collaborative studies1, we have been able to use our single-cell multi-omics data as a platform to improve analysis of spatial multi-omics data (using the Visium platform) working in the context of pancreas islets from type 1 diabetes organ donors. These studies showed us the potential value in spatial multi-omics work and how it could transform the way we think about cell:cell interactions.
As the platform and analysis strategies improve, I anticipate we as a field will learn a great deal more about the local microenvironment of HIV-infected cells and hopefully identify novel strategies to eliminate infected cells.
Throughout the CESORA sessions, I was struck by the parallel challenges faced by the different research topics compared with our work in HIV using single-cell multi-omics. The session I chaired was focused on MTb, a topic with which I am relatively familiar through collaborative studies.
It was quite clear that as the participants became more engaged during the workshop, we all were faced with similar issues in our respective fields and that we could learn from each other.
It is very important to keep asking questions, both about your own work and that of others.
For your own work, you should continually remain sceptical – are your results correct? Are you interpreting those results in the right way? How does it fit with the results obtained by others and, more broadly, how do findings in other fields influence the way you interpret your own data? How might your findings influence other fields? These moments came through for me during the CESORA conference, both during my session as well as during other sessions. There were remarkable parallels in the problems facing HIV, TB and HPV that kept arising during the conference and related discussions.
There were several aspects for me that were highlights. First, learning about the impressive efforts and infrastructure available to the CESORA team. I was unaware of the investment that has been made and even more impressed by the breadth of the collaborative group using and developing spatial multi-omics-based strategies. The focus on the next generation of researchers and African scientists was also very important. The symposium was very well attuned to this, with many talks by young scientists from Africa and beyond.
Finally, the discussions evolved over the course of the symposium as we each learned about one another’s research and expertise. Everyone there was open to each other’s ideas and happy to talk with one another. Already I have begun one collaboration with one speaker and hope to start collaborations with others.
References:
- Betts MR, et al. Spatial transcriptomics from pancreas and local draining lymph node tissue reveals a lymphotoxin-β signature in human type 1 diabetes. bioRxiv. 2025.05.19.654940; doi:10.1101/2025.05.19.654940.
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This content has been developed independently by Touch Medical Media for touchINFECTIOUS DISEASES. Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media.
Presentation: Michael Betts. Cracking the Code of tissue environments and HIV Persistence: Insights from Multi-Omics of Deep-Tissue studies. CESORA 2025.
Editor: Katey Gabrysch, Editorial Director.
Disclosures: This short article was prepared by touchINFECTIOUS DISEASES in collaboration with Michael Betts. The content was developed and edited by human editors. No fees or funding were associated with its publication. touchINFECTIOUS DISEASES utilize AI as an editorial tool (ChatGPT (GPT-4o) [Large language model]. https://chat.openai.com/chat). Mitchell Warren has nothing to disclose in relation to this interview.
Cite: Michael Betts. Unravelling HIV persistence: How tissue immunology and single-cell multi-omics are redefining the reservoir. touchINFECTIOUS DISEASES. 11 December 2025.
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