# Project 2: Revealing Viral Population and Host Environment Dynamics of SIV Tissue Reservoir

> **NIH NIH P01** · NORTHWESTERN UNIVERSITY · 2024 · $255,600

## Abstract

Despite the remarkable success of the combination antiretroviral therapy (cART) to control HIV-1 infection, viral 
reservoirs persist indefinitely under treatment. These remaining viral populations constitute the principal burden 
for an effective HIV-1 cure, as they lead to a rapid rebound in viremia when treatment fails or after analytic 
treatment interruption (ATI). Unfortunately, our understanding of the mechanisms of HIV-1 persistence during 
cART is limited because the viral reservoir population size is very small and it is established within a wide variety 
of susceptible tissues, inaccessible to evaluation. Hence these difficulties, the majority of the reservoir studies 
do not include tissue samples or study a very limited sampling of the tissue reservoirs. Therefore, we are not 
able to properly study these viral populations and their main characteristics remain unknown. Understanding the 
nature and properties of these tissue reservoirs during treatment is key to design a successful HIV-1 cure 
strategy. The team comprised by the Hope lab and Dr. Villinger has optimized and refined their 89Zr-labelled 
FAB2 probe that allows for the in vivo detection of cells expressing SIV env in an infected macaque. Using this 
approach, they have generated a new PET-CT-based workflow for the identification and downstream 
characterization of foci of SIV infection in tissues. This updated “beacon-guided system” is exquisitely sensitive 
and it is extremely powerful to find and characterize small foci of infected cells during cART or early after ATI, 
prior to any detectable viremia. These foci represent extremely rare events that are key to the understanding of 
underlying SIV biology and yet, to date, were only found through random and/or biased survey of tissue. In the 
current proposal, we intend to use the Hope lab ability to localize SIV active viremia sites in infected macaques 
and complementary genomic analysis workflows optimized by our team, to perform in-depth spatio-temporal 
studies of the reservoir viral population dynamics. We will use phylogenetic, evolutionary, and phyloanatomy 
analysis to study the characteristics tissue reservoirs. We will also assess the contribution of biological processes 
such as clonal expansion, residual viral replication, and viral production bursts in the process of reservoir 
persistence during cART. Additionally, we will analyze the characteristics and transcriptional profiles of the 
different cell types that harbor the reservoir in tissues using our multiple complementary genomic techniques. 
We will use PET-CT-guided RNAseq and PET-CT-guided spatial transcriptomics from SIV positive tissues, and 
isolate specific types of infected cells to analyze their transcriptional profiles using single-cell analysis. Due to 
Hope lab’s findings indicating that mast cells could be key in the reservoir persistence, we plan to specifically 
study the role of these mast cells in the viral population dynamics of the ...

## Key facts

- **NIH application ID:** 11082755
- **Project number:** 5P01AI169600-03
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Ramon Lorenzo-Redondo
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $255,600
- **Award type:** 5
- **Project period:** 2022-07-15 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11082755

## Citation

> US National Institutes of Health, RePORTER application 11082755, Project 2: Revealing Viral Population and Host Environment Dynamics of SIV Tissue Reservoir (5P01AI169600-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11082755. Licensed CC0.

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