@article{fa0a8d13f9254d5d8337c91f7352ec08,
title = "A genetic variation in fucosyltransferase 8 accelerates HIV-1 disease progression indicating a role for N-glycan fucosylation",
abstract = "OBJECTIVES: Core fucosylation by fucosyltransferase 8 (FUT8) is an important posttranslational modification that impacts components of the immune system. Genetic variations in FUT8 can alter its function and could, therefore, play a role in the antiviral immune response and pathogenesis of HIV-1. This study analysed the effect of a single nucleotide polymorphism (SNP) in FUT8 on the clinical course of HIV-1 infection. DESIGN/METHODS: The effect of SNPs in FUT8 on untreated HIV-1 disease outcome were analysed in a cohort of 304 people with HIV-1 (PWH) using survival analysis. Flow-cytometry was used to determine the effect of SNP on T-cell activation, differentiation and exhaustion/senescence. T-cell function was determined by proliferation assay and by measuring intracellular cytokine production. The effect of the SNP on HIV-1 replication was determined by in-vitro HIV-1 infections. Sensitivity of HIV-1 produced in PBMC with or without the SNP to broadly neutralizing antibodies was determined using a TZM-bl based neutralization assay. RESULTS: Presence of the minor allele of SNP rs4131564 was associated with accelerated disease progression. The SNP had no effect on T-cell activation and T-cell differentiation in PWH. Additionally, no differences in T-cell functionality as determined by proliferation and cytokine production was observed. HIV-1 replication and neutralization sensitivity was also unaffected by the SNP in FUT8. CONCLUSION: SNP rs4131564 in FUT8 showed a major impact on HIV-1 disease course underscoring a role for N-glycan fucosylation even though no clear effect on the immune system or HIV-1 could be determined in vitro .",
keywords = "HIV-1, clinical course, fucosyltransferase 8, pathogenesis, single nucleotide polymorphism",
author = "{van Pul}, Lisa and Irma Maurer and Boeser-Nunnink, {Brigitte D. M.} and Harskamp, {Agnes M.} and {van Dort}, {Karel A.} and Kootstra, {Neeltje A.}",
note = "Funding Information: We thank all participants in the Amsterdam Cohort Studies for their contribution. The Amsterdam Cohort Studies on HIV infection and AIDS, a collaboration between the Public Health Service Amsterdam, the Amsterdam UMC of the University of Amsterdam, Medical Center Jan van Goyen and the HIV Focus Center of the DC-Clinics, are part of the Netherlands HIV Monitoring Foundation and financially supported by the Center for Infectious Disease Control of the Netherlands National Institute for Public Health and the Environment. Funding Information: We thank all participants in the AmsterdamCohort Studies for their contribution. The AmsterdamCohort Studies on HIV infection and AIDS, a collaboration between the Public Health Service Amsterdam, the Amsterdam UMC of the University of Amsterdam, Medical Center Jan van Goyen and the HIV Focus Center of the DC-Clinics, are part of the Netherlands HIV Monitoring Foundation and financially supported by the Center for Infectious Disease Control of the Netherlands National Institute for Public Health and the Environment. We would like to thank Marit van Gils and Jonne Snitselaar for kindly providing us with the broadly neutralizing antibodies used in the neutralization assay. Author contributions: L.v.P. designed study and experiments, performed experiments, analysed and interpreted data and wrote the manuscript; I.M. performed experiments and analysed data; B.B.N. performed experiments and analysed data; A.M.H. provided materials and data management; K.v.D. performed experiments and analysed data; N.A.K. designed the study and the experiments, interpreted data, wrote the manuscript, supervised and acquired funding. Publisher Copyright: {\textcopyright} 2023 The Author(s). Published by Wolters Kluwer Health, Inc.",
year = "2023",
month = nov,
day = "1",
doi = "https://doi.org/10.1097/QAD.0000000000003689",
language = "English",
volume = "37",
pages = "1959--1969",
journal = "AIDS (London, England)",
issn = "0269-9370",
publisher = "Lippincott Williams and Wilkins",
number = "13",
}