# Host Glycomic Modulation of HIV-associated Neuro-inflammation During Viral Suppression

> **NIH NIH R01** · WISTAR INSTITUTE · 2020 · $907,453

## Abstract

PROJECT SUMMARY: Despite the widespread use of antiretroviral therapy (ART), the prevalence of neuro-
inflammation remains high and is believed to involve >40% of HIV+ individuals. This inflammatory state likely
causes cognitive dysfunction that impacts everyday functioning and increases morbidity and mortality among
ART-suppressed HIV-infected individuals. However, the physiological processes underlying this neuro-
inflammation remain poorly understood. This proposal builds on our ongoing investigation on whether glycomic
alterations in circulating glycoproteins and exosomes play a role in the pathogenesis of HIV-associated neuro-
inflammation and cognitive disorders. Our preliminary data demonstrate that higher levels of the pro-
inflammatory hypo-sialylated glycans in plasma, plasma exosomes, and cerebrospinal fluid (CSF) strongly
correlate with worse neurological impairment in HIV+ ART-suppressed individuals. However, whether glycomic
alterations drive neuro-inflammation during HIV infection remains unknown. In this project we will test the central
hypothesis that host glycomic dysregulation, in particular hypo-sialyation of circulating glycoproteins
and exosomes, contributes to neuroinflammation and the pathogenesis of HIV-associated co-
morbidities affecting the central nervous system (CNS).
 In Aim 1, we will identify the mechanism of the neuro-inflammatory effects of hypo-sialylated glycans
during ART-suppressed HIV infection. We will use hyper-sialylated and hypo-sialylated glycoproteins and
exosomes isolated from the plasma of HIV+ ART+ individuals with neurological impairments, in an ex-vivo model
of monocyte activation/inflammation and migration, in the presence or absence of glycan signaling inhibitors. In
Aim 2, we will test the hypothesis that manipulating the levels of circulating sialic acid impacts neuro-
inflammation and cognitive behavior in a mouse model of HIV-associated neurological impairment. We will use
the EcoHIV mouse model (using chimeric HIV capable of infecting mice) that was recently used as a successful
model of HIV pathogenesis and neurological impairment. Using acutely and chronically EcoHIV-infected mice
(with and without ART), that receive either a combination of sialic acid nanoparticles and sialidase inhibitors or
nude nanoparticles as controls, we will evaluate: (1) levels of cognitive impairment; (2) brain markers of
inflammation/immune activation [gene array and immunohistochemistry]; (3) EcoHIV expression in brain tissues
[qPCR]; and (4) sialylation of brain tissues and brain-derived exosomes [lectin array and flow cytometry].
 We will take advantage of recent advances in the emerging field of glycomics and an animal model of
HIV-associated neurological impairment, to clarify the inter-related mechanisms between neuro-inflammation,
cognitive dysfunction, and host immunity. Our work aims to create a new paradigm for discovering novel glycan-
based interactions that can be targeted to prevent neuro-inflamm...

## Key facts

- **NIH application ID:** 10028577
- **Project number:** 1R01NS117458-01
- **Recipient organization:** WISTAR INSTITUTE
- **Principal Investigator:** Mohamed Abdel Mohsen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $907,453
- **Award type:** 1
- **Project period:** 2020-05-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10028577

## Citation

> US National Institutes of Health, RePORTER application 10028577, Host Glycomic Modulation of HIV-associated Neuro-inflammation During Viral Suppression (1R01NS117458-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10028577. Licensed CC0.

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