# Understanding Th-monocyte interactions in HIV infection

> **NIH VA I01** · JAMES J PETERS VA  MEDICAL CENTER · 2020 · —

## Abstract

Project Summary/Abstract:
 More than 30 years after the discovery of HIV, there are still no vaccines or microbicides to prevent HIV
infection. Antiretroviral therapy (ART) is successful in suppressing virus replication, but it does not clear the
virus, offers only partial immunologic recovery, and requires lifelong adherence. A better understanding of
basic HIV–host cell interactions is needed to develop new strategies to prevent HIV infection. This proposed
study seeks to investigate the interplay of HIV with antigen-presenting cells (APCs) and helper CD4 T (Th)
cells in the presence of anti-HIV antibodies (Abs) that retard virus spread to Th cells.
 CD4 Th cells are the main cell type infected by HIV, but not all Th cells are equally vulnerable. As
compared with Th1 cells, Th17 cells are preferentially targeted by HIV, in part due to higher expression of HIV
envelope (Env) receptors, including α4β7. Our recent studies showed that Th17 cells are also preferentially
targeted by HIV transmitted from APCs. However, different outcomes arise from HIV interactions with Th cells
and distinct APCs. HIV-exposed monocytes efficiently transmit virus to Th17 cells while stimulating Th
proliferation, resulting in expansion in the number of infected Th17 cells. In contrast, virus transmission from
HIV-exposed monocyte-derived dendritic cells (MDDCs) causes the number of Th17 cells to decline. Further,
we observed that in the immunological synapses between Th cells and APCs, HIV Env enhances Th cell
activation by acting like a co-stimulatory molecule. Th cells thus co-stimulated become more permissive to HIV
infection.
 HIV Env is the key determinant that regulates virus transmission to Th cells and cellular activation of target
Th cells. HIV transmission varies depending on Env co-receptor tropisms (CCR5 vs CXCR4) and is sensitive to
interference by anti-Env Abs. HIV-induced enhancement of Th cell activation also is triggered by Env and
suppressed by anti-Env Abs. On the basis of these findings, we propose to further investigate the HIV Env
determinants influencing the efficiency of virus transmission from APCs to Th cells. Our hypothesis is that HIV
utilizes the intimate cell-cell contact between APCs and Th cells to spread to Th cells and also to enhance Th
cell activation, rendering them more permissive for virus replication, through the action of the virus Env.
Therefore, anti-Env Abs, by forming immune complexes with HIV virions, may alter APC-Th cell interactions to
blunt virus transmission and replication.
 To test these hypotheses, in Aim 1, we will define HIV Env determinants that are essential for efficient
transmission from APCs to Th cells. Monocytes and MDDCs treated with HIV will be tested as APCs in a co-
culture system to stimulate Th1 and Th17 cells and transmit viruses with distinct Envs. The Env variables to be
evaluated include co-receptor usage, N-glycan sugar composition, and affinity for α4β7 and mannose-binding
receptors. Aim 2 is to ...

## Key facts

- **NIH application ID:** 9859310
- **Project number:** 5I01BX003860-03
- **Recipient organization:** JAMES J PETERS VA  MEDICAL CENTER
- **Principal Investigator:** Catarina E Hioe
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9859310

## Citation

> US National Institutes of Health, RePORTER application 9859310, Understanding Th-monocyte interactions in HIV infection (5I01BX003860-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9859310. Licensed CC0.

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