# In vitro and in vivo analysis of macrophage-mediated clearance of HIV-1 latent reservoir

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2020 · $235,813

## Abstract

HIV-1 persists in a stable pool of latently infected resting memory CD4+ T cells. Patients on
combination antiretroviral therapy (cART) experienced plasma viral rebound after discontinuation
of cART. Current approaches to purging the latent reservoirs involve pharmacologic reactivation
of HIV-1 transcription by agents that reverse viral latency. The next step is to eliminate infected
cells in which HIV-1 gene transcription has been induced by latency reversal agents (LRAs),
which may require induction of viral-specific host immune responses. Antibodies targeting HIV-1
envelope protein can mediate killing of infected cells through antibody effector functions such as
antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis
(ADCP). Recent progress in broadly reactive neutralizing antibodies (bNAb) brought new hope to
purge the HIV-1 latent reservoirs. Antibody passive administration led to delay of virus rebound
and reduction of cell-associated viral DNA in both human and humanized mouse studies, which
was antibody Fc receptor-dependent. Combination bNAb therapy for the elimination of HIV-1
reservoirs may be a promising strategy and heavily relies on antibody Fc-dependent cytolysis or
phagocytosis of HIV-1-infected cells. Studies on how to enhance ADCC and ADCP functions may
provide major implications to the design of HIV cure strategies. While ADCC functions mediated
by NK cells have been intensively studied, the contribution of macrophages to viral reservoir
clearance has been marginalized in the past due to technical difficulties. Our preliminary results
demonstrated that blocking anti-phagocytic signal mediated by CD47/SIRPα interaction
accelerated phagocytosis of target cells express surface HIV-1 Env with the presence of HIV-1-
specific antibodies. We have also established a novel humanized mouse model of HIV-1 latency,
which support efficient reconstitution of circulating monocytes and tissue macrophages. Here we
propose to use both in vitro and in vivo models to study the role of ADCP in clearing HIV-1
reservoirs and to develop novel therapeutic strategies to enhance macrophage ADCP functions.

## Key facts

- **NIH application ID:** 9837414
- **Project number:** 5R21AI143413-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** LIANG SHAN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $235,813
- **Award type:** 5
- **Project period:** 2018-12-12 → 2020-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9837414

## Citation

> US National Institutes of Health, RePORTER application 9837414, In vitro and in vivo analysis of macrophage-mediated clearance of HIV-1 latent reservoir (5R21AI143413-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9837414. Licensed CC0.

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