Discovery of O-Linked Carbohydrate on HIV-1 Envelope and Its Role in Shielding against One Category of Broadly Neutralizing Antibodies

Silver, Zachary; Antonopoulos, Aristotelis; Haslam, Stuart M.; Dell, Anne; Dickinson, Gordon M.; Seaman, Michael S.; Desrosiers, Ronald C.

doi:10.1016/j.celrep.2020.01.056

Cited by 32 publications

(29 citation statements)

References 30 publications

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“…Among the four newly discovered O-glycosylation sites, two reside in the furin cleavage site between S1/S2 (Thr678 and Ser686) which are unique to SARS-CoV-2. Although there has not yet been evidence that O-glycosylation plays a role in protease cleavage of S 1 , 29 , further investigation is warranted as O-glycosylation does affect protease susceptibility in other systems, as well as antibody recognition 30 , 31 .…”

Section: Resultsmentioning

confidence: 99%

SARS-CoV-2 Spike Protein Interacts with Multiple Innate Immune Receptors

Gao

Zeng

Jia

et al. 2020

Preprint

111

149

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The spike (S) glycoprotein in the envelope of SARS-CoV-2 is densely glycosylated but the functions of its glycosylation are unknown. Here we demonstrate that S is recognized in a glycan-dependent manner by multiple innate immune receptors including the mannose receptor MR/CD206, DC-SIGN/CD209, L-SIGN/CD209L, and MGL/CLEC10A/CD301. Single-cell RNA sequencing analyses indicate that such receptors are highly expressed in innate immune cells in tissues susceptible to SARS-CoV-2 infection. Binding of the above receptors to S is characterized by affinities in the picomolar range and consistent with S glycosylation analysis demonstrating a variety of N- and O-glycans as receptor ligands. These results indicate multiple routes for SARS-CoV-2 to interact with human cells and suggest alternative strategies for therapeutic intervention.

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Section: Resultsmentioning

confidence: 99%

SARS-CoV-2 Spike Protein Interacts with Multiple Innate Immune Receptors

Gao

Zeng

Jia

et al. 2020

Preprint

111

149

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“…It remains to be addressed what physiological role these responses may have in in vivo HIV control. As shown recently, inhibition of glycosylation in HIV producing cells leads to massive increase in virus replication; suggesting that the glycosylation of viral proteins comes at some fitness costs while possibly protecting from immune surveillance (46,68). It will be interesting to assess the balance between such reduced replication fitness and the ability to use glycosylation as an escape strategy to avoid T cell immunity (if at all occurring in vivo) in future research.…”

Section: Future Perspectivesmentioning

confidence: 91%

“…To date, most studies on HIV protein glycosylation have been focused on the envelope protein (Env) and its relationship with viral escape from humoral immunity (45). As other viruses, HIV is highly dependent on the host cellular machinery and extensive glycosylation of viral proteins has been documented (18,23,46,47). In addition, there are several reports that suggest that HIV could interfere with the host glycosylation machinery (45,(48)(49)(50)(51)(52)(53)(54), but only two (19,21) describe T cell responses to glycosylated epitopes.…”

Section: Does Glycosylation Have An Impact On Epitope Presentation?mentioning

confidence: 99%

Does Antigen Glycosylation Impact the HIV-Specific T Cell Immunity?

et al. 2021

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It is largely unknown how post-translational protein modifications, including glycosylation, impacts recognition of self and non-self T cell epitopes presented by HLA molecules. Data in the literature indicate that O- and N-linked glycosylation can survive epitope processing and influence antigen presentation and T cell recognition. In this perspective, we hypothesize that glycosylation of viral proteins and processed epitopes contribute to the T cell response to HIV. Although there is some evidence for T cell responses to glycosylated epitopes (glyco-epitopes) during viral infections in the literature, this aspect has been largely neglected for HIV. To explore the role of glyco-epitope specific T cell responses in HIV infection we conducted in silico and ex vivo immune studies in individuals with chronic HIV infection. We found that in silico viral protein segments with potentially glycosylable epitopes were less frequently targeted by T cells. Ex vivo synthetically added glycosylation moieties generally masked T cell recognition of HIV derived peptides. Nonetheless, in some cases, addition of simple glycosylation moieties produced neo-epitopes that were recognized by T cells from HIV infected individuals. Herein, we discuss the potential importance of these observations and compare limitations of the employed technology with new methodologies that may have the potential to provide a more accurate assessment of glyco-epitope specific T cell immunity. Overall, this perspective is aimed to support future research on T cells recognizing glycosylated epitopes in order to expand our understanding on how glycosylation of viral proteins could alter host T cell immunity against viral infections.

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“…The decrease in antigenic drift reflects reduced selective pressure for the virus to produce mutation and this is attributed to the function of the glycan to “shield” the region from immune pressure. While the majority of this work has focused on N‐glycosylation, glycoshielding has also been attributed to O‐glycosylation such as in HIV‐1 gp120 (Silver et al, 2020). As the density of glycosites increase so does the analytical challenge.…”

Section: Important Functional Targets Of Glycomics Analysis In the VImentioning

confidence: 99%

Glycomics and glycoproteomics of viruses: Mass spectrometry applications and insights toward structure–function relationships

Cipollo

Parsons

2020

Mass Spectrometry Reviews

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The advancement of viral glycomics has paralleled that of the mass spectrometry glycomics toolbox. In some regard the glycoproteins studied have provided the impetus for this advancement. Viral proteins are often highly glycosylated, especially those targeted by the host immune system. Glycosylation tends to be dynamic over time as viruses propagate in host populations leading to increased number of and/or “movement” of glycosylation sites in response to the immune system and other pressures. This relationship can lead to highly glycosylated, difficult to analyze glycoproteins that challenge the capabilities of modern mass spectrometry. In this review, we briefly discuss five general areas where glycosylation is important in the viral niche and how mass spectrometry has been used to reveal key information regarding structure–function relationships between viral glycoproteins and host cells. We describe the recent past and current glycomics toolbox used in these analyses and give examples of how the requirement to analyze these complex glycoproteins has provided the incentive for some advances seen in glycomics mass spectrometry. A general overview of viral glycomics, special cases, mass spectrometry methods and work‐flows, informatics and complementary chemical techniques currently used are discussed. © 2020 The Authors. Mass Spectrometry Reviews published by John Wiley & Sons Ltd. Mass Spec Rev

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Discovery of O-Linked Carbohydrate on HIV-1 Envelope and Its Role in Shielding against One Category of Broadly Neutralizing Antibodies

Abstract: Highlights d A subset of HIV-1 isolates possess O-linked carbohydrate on their Envelope glycoprotein d This O-glycosylation is preferentially found on strains with unusually long V1 domains d These O-glycans shield the virus from V3-glycan broadly neutralizing antibodies

Cited by 32 publications

References 30 publications

SARS-CoV-2 Spike Protein Interacts with Multiple Innate Immune Receptors

SARS-CoV-2 Spike Protein Interacts with Multiple Innate Immune Receptors

Does Antigen Glycosylation Impact the HIV-Specific T Cell Immunity?

Glycomics and glycoproteomics of viruses: Mass spectrometry applications and insights toward structure–function relationships

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