Hepatitis C virus modulates IgG glycosylation in HIV co-infected antiretroviral therapy suppressed individuals.

ABSTRACT

OBJECTIVE: Glycosylation plays a critical role in mediating several antibody (mainly immunoglobulin G; IgG) immunological functions, including antibody-dependent cell-mediated cytotoxicity (ADCC), and anti-inflammatory activities. We investigated whether IgG glycosylation and immune profile patterns are differentially modulated in mono and dual infection using samples from untreated hepatitis C virus (HCV)-infected individuals with and without co-infection with antiretroviral therapy (ART)-suppressed HIV. DESIGN: IgG glycosylation, immune subsets, natural killer cell function, and liver enzymes were assessed in 14 HCV mono-infected and 27 ART-suppressed HIV/HCV co-infected participants naïve to HCV treatment. Historic IgG glycosylation data from 23 ART-suppressed chronically HIV-infected individuals were also used for comparisons. METHODS: Plasma IgG glycosylation was assessed using capillary electrophoresis. Whole blood was used for immune subset characterization by flow cytometry. Peripheral blood mononuclear cells were used to measure constitutive and interferon-α-induced K562 target cell lysis. Statistical analysis was performed using R (3.5.0). RESULTS: HIV/HCV had lower levels of pro-ADCC-associated nonfucosylated glycans when compared with HIV [e.g. di-sialylated A2 percentage (%) P = 0.04], and higher levels of T and myeloid cell activation/exhaustion when compared with HCV (e.g. CD3CD8CD38 % P < 0.001). Finally, in HCV high levels of the anti-inflammatory galactosylated and sialylated glycans were associated with low plasma levels of aspartate aminotransferase (AST), low CD8 T-cell activation, and high CD8 T-cell exhaustion. CONCLUSION: HCV modulates IgG glycosylation profile in HIV co-infected individuals on suppressive ART. These results could inform on the modulation of IgG glycans in other mono and dual infections.