# Host Glycomic Determinants of HIV Persistence in vivo

> **NIH NIH R21** · WISTAR INSTITUTE · 2020 · $223,250

## Abstract

PROJECT SUMMARY. A comprehensive understanding of host factors driving the formation and maintenance
of the latent HIV reservoir during suppressive antiretroviral therapy (ART) is imperative for developing cure
strategies. We have been taking advantage of work in the emerging field of glycomics (the discipline of defining
the structures and functional roles of glycans in biological systems) to understand how glycosylation of circulating
(plasma) glycoproteins, including antibodies (IgGs), contributes to HIV persistence during ART. Accumulating
evidence suggests that glycan profiles mediate and drive several immunological functions, e.g. higher antibody-
dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and anti-
inflammatory activities. In our recent publication, we identified certain host glycomic traits that inform chronic
inflammation, immune activation, and levels of nucleic acid-based measures of HIV reservoir in vivo: (1) Levels
of certain mono- and di-galactosylated non-fucosylated glycomic traits negatively correlate with levels of
CD4+ T cell-associated total HIV DNA and RNA during suppressive ART; these particular traits have been
associated with higher ADCC and ADCP activities. (2) Levels of sialylated (anti-inflammatory) glycans
negatively associate with HIV infection, irrespective of long-term suppressive ART, and are associated with
higher levels of CD4+ T cells and lower levels of immune inflammation/activation during suppressive ART. Our
findings provide the first proof-of-concept evidence that glycomic alterations known to be linked to different states
of inflammation and immune functionality are also associated with several immunologic and virologic measures
of HIV persistence. Together, these data allow us to hypothesize that levels of certain circulating glycomic
signatures (in particular, galactosylated and sialylated glycomic traits) reflect differential states of viral
control, which relate to HIV reservoir size during ART and viral rebound upon ART cessation.
 We will be taking advantage of banked samples from HIV+ individuals on suppressive ART, who
completed an Analytical Treatment Interruption (ATI) study, with documented data on time-to-rebound and viral
setpoint upon the cessation of ART. Glycomic profiles will be obtained using advanced glycomic technologies
and used in both Aims. In Aim 1: we will determine if levels of sialylated and galactosylated antibody and plasma
glycans are linked to the size of HIV reservoir (estimated as post-ATI time-to-rebound and viral load set points).
In Aim 2: we will define whether the observed antibody galactosylation profiles are simply biomarkers of disease
state or whether they also contribute to viral control during ART and/or upon ART cessation, by influencing
plasma-mediated innate immune effector ADCC and ADCP activities. We will examine 1) the relationship
between antibody glycosylation and antibody-mediated ADCC and ADCP activitie...

## Key facts

- **NIH application ID:** 9900757
- **Project number:** 5R21AI143385-02
- **Recipient organization:** WISTAR INSTITUTE
- **Principal Investigator:** Mohamed Abdel Mohsen
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $223,250
- **Award type:** 5
- **Project period:** 2019-04-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9900757

## Citation

> US National Institutes of Health, RePORTER application 9900757, Host Glycomic Determinants of HIV Persistence in vivo (5R21AI143385-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9900757. Licensed CC0.

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