Jennifer Zerbato

This session, chaired by Zhiwei Chen, examined defining characteristics of proviral integration sites, specifically of intact proviruses, and rebound virus following a treatment interruption.

Dr. Linos Vandekerckhove described that in PWH on ART, the source of viral rebound following ATI was heterogeneous, coming from different cell subsets and tissues. Moreover, intact proviruses were enriched in genes for zinc finger nucleases (ZFN), particularly KRAB-ZFN family, which may be a potential hotspot for intact clones. Dr. Beatrice Hahn identified key characteristics of rebound viruses driven by host innate immune responses. Rebound viruses from CD4 T cells were highly resistant to IFN and autologous neutralizing antibodies, whereas those rebound from macrophages were not. This suggests that the main cells contributing to viral rebound are CD4. Dr. Xu Yu demonstrated that elite controllers (EC) had significantly smaller proviral loads than PWH on ART and less intact HIV DNA, highlighting the importance of proviral quality instead of quantity. Intact proviruses from EC were enriched in satellite DNA or gene deserts, meaning that they are likely in deep latency.

This was a great session highlighting the importance of proviral sequencing and the need for further characterization of viral reservoirs, and perhaps just as importantly, rebound virus following a treatment interruption. There are continuously emerging technologies that are helping expand our ability to understand how and where HIV integrates into the genome, how and where HIV may reactivate, or how HIV may evade innate immune responses, including MIP-seq, FLIP-seq, and multiple-displacement amplification, all of which were highlighted in this session. The biggest takeaway message from this session was that when it comes to integration sites and reservoir characterization, location matters.