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Interferon-? alters host glycosylation machinery during treated HIV infection.

ABSTRACT: BACKGROUND:A comprehensive understanding of host factors modulated by the antiviral cytokine interferon-? (IFN?) is imperative for harnessing its beneficial effects while avoiding its detrimental side-effects during HIV infection. Cytokines modulate host glycosylation which plays a critical role in mediating immunological functions. However, the impact of IFN? on host glycosylation has never been characterized. METHODS:We assessed the impact of pegylated IFN?2a on IgG glycome, as well as CD8+ T and NK cell-surface glycomes, of 18 HIV-infected individuals on suppressive antiretroviral therapy. We linked these glycomic signatures to changes in inflammation, CD8+ T and NK cell phenotypes, and HIV DNA. FINDINGS:We identified significant interactions that support a model in which a) IFN? increases the proportion of pro-inflammatory, bisecting GlcNAc glycans (known to enhance Fc?R binding) within the IgG glycome, which in turn b) increases inflammation, which c) leads to poor CD8+ T cell phenotypes and poor IFN?-mediated reduction of HIV DNA. Examining cell-surface glycomes, IFN? increases levels of the immunosuppressive GalNAc-containing glycans (T/Tn antigens) on CD8+ T cells. This induction is associated with lower HIV-gag-specific CD8+ T cell functions. Last, IFN? increases levels of fucose on NK cells. This induction is associated with higher NK functions upon K562 stimulation. INTERPRETATION:IFN? causes host glycomic alterations that are known to modulate immunological responses. These alterations are associated with both detrimental and beneficial consequences of IFN?. Manipulating host glycomic interactions may represent a strategy for enhancing the positive effects of IFN? while avoiding its detrimental side-effects. FUNDING:NIH grants R21AI143385, U01AI110434.

SUBMITTER: Giron LB

PROVIDER: S-EPMC7452630 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Interferon-α alters host glycosylation machinery during treated HIV infection.

Giron Leila B LB Colomb Florent F Papasavvas Emmanouil E Azzoni Livio L Yin Xiangfan X Fair Matthew M Anzurez Alitzel A Damra Mohammad M Mounzer Karam K Kostman Jay R JR Tebas Pablo P O'Doherty Una U Tateno Hiroaki H Liu Qin Q Betts Michael R MR Montaner Luis J LJ Abdel-Mohsen Mohamed M

EBioMedicine 20200819

<h4>Background</h4>A comprehensive understanding of host factors modulated by the antiviral cytokine interferon-α (IFNα) is imperative for harnessing its beneficial effects while avoiding its detrimental side-effects during HIV infection. Cytokines modulate host glycosylation which plays a critical role in mediating immunological functions. However, the impact of IFNα on host glycosylation has never been characterized.<h4>Methods</h4>We assessed the impact of pegylated IFNα2a on IgG glycome, as ...[more]

PMID: 32827942

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Interferon-? alters host glycosylation machinery during treated HIV infection.

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Interferon-α alters host glycosylation machinery during treated HIV infection.

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