# Defining HIV Env protein expression in latently infected cells

> **NIH NIH R21** · GEORGE WASHINGTON UNIVERSITY · 2024 · $201,875

## Abstract

Project Summary/Abstract
Advances in B cell biology and molecular virology have enabled the discovery, characterization, and commercial
development of broadly neutralizing antibodies (bNAbs). They are a promising immunotherapy that can be
incorporated in many strategies for the treatment and/or cure of HIV-1. Antibodies have many effector functions
beyond neutralization and their most important mechanism of action for treatment/cure may be their ability to
opsonize infected cells, tagging them for antibody-dependent cellular cytotoxicity or phagocytosis (ADCC/ADCP)
by immune effector cells. It is not clear that bNAbs are mediating clearance of infected cells in clinical trials when
they are passively infused into chronically infected people living with HIV (PLWH). An obvious reason for this
lack of efficacy of bNAbs may be a lack of Env protein expression while on suppressive ART. Our lack of
knowledge about the level of Env expression during HIV latency and latency reversal prevents effective use of
bNAbs as therapeutics. To address this gap, the ability to detect low level Env protein expression in cells infected
with different subtypes of HIV-1 is needed. The Bosque lab has published an ultrasensitive method to detect p24
Gag protein down to the fg/ml level and has preliminary data for a newly developed Env assay. Here we propose
to use these assays to detect low levels of Env and Gag protein in a well-described model of latency and compare
the data to Env surface expression as measured by flow cytometry (Aim 1). Within these assays, we have the
flexibility to test Env detection using bNAbs targeting different epitopes to probe for Env conformation (i.e., trimer,
monomer, etc) and extend these analyses to diverse HIV isolates from different subtypes to measure differences
in Env expression and latency attributable to genetically diverse virus (Aim 2). Knowing these crucial factors
about Env and Gag expression in a carefully controlled model of latency will allow us to further investigate HIV
protein translation in future studies using cohorts of PLWH. These studies will improve the ability of therapeutics
using Env-targeting strategies to target latently infected cells.

## Key facts

- **NIH application ID:** 10899580
- **Project number:** 5R21AI179423-02
- **Recipient organization:** GEORGE WASHINGTON UNIVERSITY
- **Principal Investigator:** Alberto Bosque
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $201,875
- **Award type:** 5
- **Project period:** 2023-08-04 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10899580

## Citation

> US National Institutes of Health, RePORTER application 10899580, Defining HIV Env protein expression in latently infected cells (5R21AI179423-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10899580. Licensed CC0.

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