# Harnessing CD89+ NK Cells for Novel Therapeutic Interventions Against HIV/SIV

> **NIH NIH R21** · DUKE UNIVERSITY · 2024 · $217,350

## Abstract

While antiretroviral therapy (ART) can control the replication of human immunodeficiency virus (HIV) and delay
disease progression, there is still no cure, and HIV remains a global public health challenge. A better
understanding of early and persistent immunological events in HIV infection is critical to inform novel
interventions. The majority of current strategies aiming to prevent, control or eradicate HIV rely on harnessing
effector functions of cytotoxic T cells, helper T cells, B cells and antibodies to attack HIV and HIV-infected cells.
However, natural killer (NK) cells might represent another subset for therapeutic modulation. Recently, our lab
has carried out in-depth, yet preliminary research into NK cells expressing the IgA receptor, CD89, using both
human and nonhuman primate samples. We have generated preliminary data showing that: (i) CD89+ NK cells
can be readily identified in various tissues including peripheral blood and mucosal tissues; (ii) CD89+ NK cells
display an altered signaling phenotype compared to CD89- NK cells; (iii) CD89+ NK cells are significantly
restricted in their activation potential; and (iv) CD89+ NK cells can be identified through multiplex imaging
indicating their relevant proximity in the GI mucosae. Collectively these data form the basis for our overarching
hypothesis that CD89 acts as an inhibitory checkpoint to regulate NK cell mucosal functions, and, therefore, may
serve as an attractive target for NK cell-based interventions and therapeutics in lentivirus infections. We will test
this hypothesis through two focused Exploratory Aims: (i) Characterize the role(s) and functional regulation
of CD89+ NK in the mucosae in normal and SIV/SHIV-infected macaques; and (ii) Investigate the role of
autologous CD89+ NK cells in therapeutic modulation of SIV infection. Ultimately, this knowledge has the
potential to inform strategies to tune CD89+ NK cells for preventive or therapeutic interventions and personalized
treatments, vaccine development, and strategies for reducing viral reservoirs.

## Key facts

- **NIH application ID:** 10937151
- **Project number:** 1R21AI184422-01
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Roger Keith Reeves
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $217,350
- **Award type:** 1
- **Project period:** 2024-08-13 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10937151

## Citation

> US National Institutes of Health, RePORTER application 10937151, Harnessing CD89+ NK Cells for Novel Therapeutic Interventions Against HIV/SIV (1R21AI184422-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10937151. Licensed CC0.

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