# Host-Dependent Mechanisms that Guide the Longitudinal Dynamic of Sites of SIV Integration

> **NIH NIH DP2** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2024 · $500,475

## Abstract

Project Summary
HIV integrates into the host genome and enters a state of latency, enabling infected cells to
escape immune recognition and clearance. Eliminating the latent reservoir will require an
understanding of the early host mechanisms that regulate latency establishment and
mechanisms that reinforce latency during ART suppression. This can be achieved by
investigating three major questions: provirus integration preferences, the “where.” The host
mechanisms that regulate proviral integration, the “how.” The effect of integration on the host
transcriptional and epigenetics programs.
There is growing evidence of the host's early factors, including the levels of metabolites of host
and commensal bacteria origin, specific cytokines, or frequencies of activated innate and
adaptive immune cells in modulating key host immune mechanisms that could promote disease
progression and increase susceptibility to infection as a result of heightened levels of immune
homeostasis and effector function perturbation. However, our knowledge of the host early
mechanisms that regulate SIV integration and the impact of integration on the overall host
immune system is poorly understood.
In this proposal, I will leverage existing samples collected from SIV-infected ART-suppressed
rhesus macaques at baseline (pre-infection), before ART initiation, and during ART suppression
to generate an ATLAS of SIV integration sites. In these animals, we observed a significant
dynamic range of integrated SIV DNA before ART initiation, suggesting that host factors could
be responsible for the heterogeneity of the replication-competent SIV reservoir. To delineate the
impact of the host factors on the SIV integration, we will use single-cell assays that capture host
gene expression and chromatin accessibility, as well as plasma levels of cytokines and
metabolites of the host and commensal bacteria to characterize the mechanisms triggered early
in infection by host factors that regulate SIV integration and determine how SIV integration
impacts the host transcriptome and epigenome.
The outcome of this study could uncover intricate mechanisms by which the host's immune
system influences SIV integration and how integration, in turn, shapes the host gene expression
and immune functions. These insights can pave the way for innovative therapeutic strategies to
prevent viral integration or reverse host immune dysfunction, ultimately offering new possibilities
for HIV cure research.

## Key facts

- **NIH application ID:** 10950590
- **Project number:** 1DP2AI184811-01
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Malika Boudries
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $500,475
- **Award type:** 1
- **Project period:** 2024-08-15 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10950590

## Citation

> US National Institutes of Health, RePORTER application 10950590, Host-Dependent Mechanisms that Guide the Longitudinal Dynamic of Sites of SIV Integration (1DP2AI184811-01). Retrieved via AI Analytics 2026-06-13 from https://api.ai-analytics.org/grant/nih/10950590. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*