# Mechanisms of Natural Killer Cell Clearance of SIV from Lymphoid Follicles

> **NIH NIH R01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2020 · $620,422

## Abstract

Despite efficient suppression of plasma viremia in HIV-infected patients on cART, replication competent
virus is still recoverable from a variety of anatomic sites. A major reservoir of HIV and pathogenic SIV infection
in rhesus macaques (RM) are lymph node follicles (via replication in TFH cells and viral trapping by FDC) that
generally prohibit access to cytotoxic CD8+ T cells. Interestingly, nonpathogenic SIV infection of African green
monkeys (AGM) exhibits high viral loads in blood and the gut mucosae, but lacks virus in lymphoid follicles.
Natural killer (NK) cells provide rapid early responses to HIV/SIV infections and contribute substantially to
disease modulation and vaccine protection, but the underlying mechanisms for NK cell surveillance and
modulation of HIV/SIV reservoirs is unclear. Our recent research indicates that SIV can be effectively cleared
from lymphoid follicles in nonpathogenic AGM but not pathogenic RM hosts and is dependent on an IL-15-
dependent redistribution of NK cells to lymph node follicles and increased CXCR5 expression on AGM NK
(Huot et al. Nature Medicine 2017). In this innovative proposal we will utilize three SIV-infected nonhuman
primate models to test the central hypothesis that NK cells critically contribute to the reduction of SIV
reservoirs. Specifically we will: (1) Determine mechanisms associated with NK cell-mediated control of
SIV reservoirs; and (2) Determine mechanisms associated with NK cell failure to control SIV reservoirs
in lymph nodes and associated pathogenesis. Application of these data could contribute substantially to
future HIV/SIV vaccines, immunotherapeutics, or reservoir purging strategies that harness the potent antiviral
potential of NK cells.

## Key facts

- **NIH application ID:** 9823862
- **Project number:** 5R01AI143457-02
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Roger Keith Reeves
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $620,422
- **Award type:** 5
- **Project period:** 2018-12-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9823862

## Citation

> US National Institutes of Health, RePORTER application 9823862, Mechanisms of Natural Killer Cell Clearance of SIV from Lymphoid Follicles (5R01AI143457-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9823862. Licensed CC0.

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