Breaking the Glyco-Code of HIV Persistence and Immunopathogenesis

Abstract

Purpose of review: Glycoimmunology is an emerging field focused on understanding how immune responses are mediated by glycans (carbohydrates) and their interaction with glycanbinding proteins called lectins. How glycans influence immunological functions is increasingly well understood. In a parallel way, in the HIV field, it is increasingly understood how the host immune system controls HIV persistence and immunopathogenesis. However, what has mostly been overlooked, despite its potential for therapeutic applications, is the role that the host glycosylation machinery plays in modulating the persistence and immunopathogenesis of HIV.Here, we will survey four areas in which the links between glycan-lectin interactions and immunology, and between immunology and HIV are well described. For each area, we will describe these links and then delineate the opportunities for the HIV field in investigating potential interactions between glycoimmunology and HIV persistence/immunopathogenesis. Recent findings:Recent studies show that the human glycome (the repertoire of human glycan structures) plays critical roles in driving or modulating several cellular processes and immunological functions that are central to maintaining HIV infection.

Associations Between Plasma Immunomodulatory and Inflammatory Mediators With VACS Index Scores Among Older HIV-Infected Adults on Antiretroviral Therapy

“…Glycan-glycan-binding protein mediated immune responses, particularly through the galectin family of proteins, is an emerging field in HIV research and implicated to play a role in HIV pathogenesis ( 67 ). Gal-9 and Gal-1, are demonstrated as drivers of HIV transcription and cell entry, respectively, as well as pro-inflammatory mediators ( 33 – 35 , 37 , 38 ).…”

Glycan Microarrays as Chemical Tools for Identifying Glycan Recognition by Immune Proteins

“…With thousands of publications every year, it fundamentally impacts many aspects of biomedical sciences and has led to fascinating breakthroughs in a large number of biomedical areas, including primary immunodeficiencies, immunometabolism, neuroimmunology, mucosal immunology, cancer immunotherapy, and vaccine development. It is becoming increasingly clear that major components of our immune system include glycoproteins and recognition of glycans by glycan-binding proteins (GBPs) or lectins (Rabinovich et al, 2012;Colomb et al, 2019;Läubli and Varki, 2019;Pascoal et al, 2019;Taylor and Drickamer, 2019). These components are involved in all aspects of cellular recognition and signaling, both biological and pathological.…”

Non-Invasive Plasma Glycomic and Metabolic Biomarkers of Post-treatment Control of HIV

“…For example, antibody glycans can alter an antibody's Fc-mediated innate immune functions, including ADCC and several pro-and anti-in ammatory activities. [22][23][24][25] Among glycans on antibodies, the presence of core fucose results in a weaker binding to Fcγ receptor IIIA and reduces ADCC. 73 The same occurs with terminal sialic acid, which reduces ADCC.…”

“…[16][17][18][19][20][21] In addition, glycans on circulating glycoproteins have functional signi cance, as they play essential roles in mediating immunological functions, including antibody-dependent cell-mediated cytotoxicity (ADCC) and pro-and anti-in ammatory activities. [22][23][24][25] Similarly, plasma metabolites have been investigated as diagnostic and prognostic biomarkers in several diseases such as heart disease, 26 hepatitis, 27 Alzheimer's disease, 28 and cancer. 29,30 Similar to plasma glycans, plasma metabolites are biologically active molecules that function to regulate critical immunological responses, including in ammatory responses.…”