# Identification of SIV replication and reservoirs in the CNS

> **NIH NIH R01** · UNIVERSITY OF LOUISIANA AT LAFAYETTE · 2024 · $784,326

## Abstract

Abstract
Even though highly potent antiretroviral therapy (ART) has the ability to reduce viral replication to undetectable
levels in the plasma in simian immunodeficiency virus (SIV) infected monkeys, our recently developed viral env
directed immunoPET/CT imaging technology has been able to detect foyers of continued SIV signals even after
prolonged ART. However, the ability of this non-invasive technique to map SIV signal in the CNS have thus far
been elusive. In this application we propose to focus on the development of probes and strategies to specifically
address SIV signals in the CNS, by optimizing the technology to enable SIV specific PET probes to cross the
blood brain barrier and mark cells expressing SIV env in vivo. Towards this goal we will use the pigtailed
macaque model infected with SIVsmB670/SIVmac239-17E-Fred developed and validated by the team of Dr.
Clements as one of the most reliable models of neuroHIV. Leveraging the strength and technological advances
available at the New Iberia Research Center and Georgia Tech, we will map the seeding of reservoirs in the
CNS during acute infection and monitor the kinetic of viral signals post-acute infection using a combination of
immunoPET/CT, light-sheet and confocal imaging techniques, as well as sorting of infected cells to document
the nature and function of cells remaining active in the early chronic phase of CNS SIV infection. Next we will
document the dynamics of viral kinetics in the CNS relative to total body upon ART initiation, as well as post-
ART interruption. Data generated from these highly detailed analyses will delineate which cells retain persistent
viral replication under ART (if any) and more importantly evaluate the contribution of CNS viral reservoirs to the
early viral rebound in vivo. The in depth analysis of this data will also provide important steps towards the
development of cure strategies that include the CNS.

## Key facts

- **NIH application ID:** 10906149
- **Project number:** 5R01MH125395-05
- **Recipient organization:** UNIVERSITY OF LOUISIANA AT LAFAYETTE
- **Principal Investigator:** PHILIP J SANTANGELO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $784,326
- **Award type:** 5
- **Project period:** 2020-09-19 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10906149

## Citation

> US National Institutes of Health, RePORTER application 10906149, Identification of SIV replication and reservoirs in the CNS (5R01MH125395-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10906149. Licensed CC0.

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