# Development and Use of Novel SHIVs Bearing Clinically Relevant HIV-1 Envs for Examining HIV Persistence and Eradication in the CNS of Nonhuman Primates

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $677,839

## Abstract

PROJECT SUMMARY/ABSTRACT
In untreated infection, HIV-1 can establish populations in the CNS, often in long-lived myeloid lineage cells.
Examining these tissue reservoirs in antiretroviral therapy (ART)-suppressed humans is rarely possible; creating
a need for a nonhuman primate (NHP) model that recapitulates many of the features of NeuroHIV in humans.
The objective of this study is to develop, and use, a novel simian-human immunodeficiency virus (SHIV) model
to examine viral persistence in the CNS during ART and to determine whether CNS reservoirs contribute to viral
rebound when ART is stopped. This model will generate CNS disease at a moderate pace, similar to that
observed in HIV-infected humans, rather than the extremely rapid pace of most SIV models of NeuroAIDS. We
have generated replication competent novel SHIV clones carrying eight different HIV-1 envs, each of which was
cloned from either the human CNS, where it was adapted to replicating in myeloid lineage cells (M-SHIVs), or
from the human blood, where it was adapted to replicating in CD4+ T cells (R5 T-SHIVs). In addition, we have
incorporate newly discovered mutations in env that greatly increase SHIV replication in rhesus macaques. In
vivo competition experiments will be used to identify SHIVs that replicate robustly and establish viral populations
in the CNS within 1 year of infection (Aim 1). High fitness SHIVs will then be used to test the hypothesis that M-
and R5 T-SHIVs are both able to establish reservoirs that persist during ART, but that M-SHIV reservoirs will
primarily be found in the CNS, while R5 T-SHIV reservoirs will primarily be found in T cell-rich tissues (lymph
nodes and gut) (Aim 2). We will then examine the contribution that these variants make to viral rebound after
ART interruption (Aim 3). Successful completion of these aims will both establish a realistic model of HIV-1 CNS
disease that can be applied to future studies of eradication and it will expand our knowledge of viral persistence
in the CNS by identifying the types of infected cells that persistent during antiretroviral therapy and whether these
cells persist as latent or actively replicating reservoirs.

## Key facts

- **NIH application ID:** 10018109
- **Project number:** 5R01MH118990-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** SARAH BETH JOSEPH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $677,839
- **Award type:** 5
- **Project period:** 2019-09-16 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10018109

## Citation

> US National Institutes of Health, RePORTER application 10018109, Development and Use of Novel SHIVs Bearing Clinically Relevant HIV-1 Envs for Examining HIV Persistence and Eradication in the CNS of Nonhuman Primates (5R01MH118990-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10018109. Licensed CC0.

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