# Sialic Acid Modulation of HIV-associated Chronic Inflammaging

> **NIH NIH R01** · WISTAR INSTITUTE · 2022 · $506,186

## Abstract

PROJECT SUMMARY: An HIV-associated state of chronic inflammation persists despite antiretroviral therapy
(ART) and is termed ‘inflammaging’. Such inflammation is a significant contributor to the increased risk HIV+
individuals’ experience of age- and HIV-associated co-morbidities. However, the physiological processes
underlying it remain poorly understood. We have been investigating whether glycomic alterations in circulating
glycoproteins play a role in the pathogenesis of inflammation in HIV+ individuals. Glycan alterations, in particular,
loss of sialic acid (hypo-sialylation), on circulating glycoproteins are known to mediate inflammation and
associate with biological age. In a recent publication, we found that levels of circulating, anti-inflammatory
sialylated glycoproteins and immunoglobulins G (IgGs) are markedly reduced in the plasma of HIV+ individuals
(viremic and ART-suppressed) compared to HIV- controls. This was intriguing because sialylated glycoproteins
are known to initiate an anti-inflammatory response, possibly by inhibiting TLR4 signaling. Testing for a
connection with co-morbidities, we found that levels of hypo-sialylation significantly correlate with the prevalence
of several inflammation-associated co-morbidities in HIV+ ART+ individuals. These data support our
hypothesis that HIV infection accelerates the pace of age-associated hypo-sialyation, which contributes
to inflammaging. Consistent with the work of others suggesting that hypo-sialyation not only correlates with
inflammation, but also mechanistically drive it, we showed that sialic-acid coated nanoparticles reduce immune
activation/inflammation in the physiologically-relevant BLT humanized mouse model of HIV infection. We posit
that normalizing glycosylation patterns will prevent the development of HIV-associated inflammation. In
Aim 1 we will test the hypothesis that age-associated hypo-sialylation of circulating glycoproteins and IgGs is
accelerated in HIV+ individuals compared to HIV- counterparts and is linked to inflammaging. We will use
advanced glycomic technologies and well-powered, cross-sectional, and longitudinal plasma samples from well-
characterized cohorts of HIV (WIHS and MACS), to establish a longitudinal relationship between glycomic
profiles, aging with HIV, inflammation, and the prevalence of subclinical atherosclerosis (as an example of
inflammation-associated co-morbidity). We also will test the hypothesis that enhanced activity of sialidase
underlies the hypo-sialyation observed in HIV+ ART+ individuals. In Aim 2, we will test the hypothesis that sialic
acid coated nanoparticles can prevent immune activation/inflammation during ART-suppressed HIV infection,
using HIV-infected, ART-suppressed BLT humanized mice. We will also test if these effects are mediated by
inhibiting TLR4 signaling. We are taking advantage of recent advances in the emerging field of glycomics to
clarify the association between HIV, aging, and the host immune environment ...

## Key facts

- **NIH application ID:** 10379232
- **Project number:** 5R01AG062383-04
- **Recipient organization:** WISTAR INSTITUTE
- **Principal Investigator:** Mohamed Abdel Mohsen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $506,186
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10379232

## Citation

> US National Institutes of Health, RePORTER application 10379232, Sialic Acid Modulation of HIV-associated Chronic Inflammaging (5R01AG062383-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10379232. Licensed CC0.

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