Benzyl-2-Acetamido-2-Deoxy-α-d-Galactopyranoside Increases Human Immunodeficiency Virus Replication and Viral Outgrowth Efficacy In Vitro

Frontiers in Immunology
Alex OlveraChristian Brander

Abstract

Glycosylation of host and viral proteins is an important posttranslational modification needed to ensure correct function of glycoproteins. For this reason, we asked whether inhibition of O-glycosylation during human immunodeficiency virus (HIV) in vitro replication could affect HIV infectivity and replication rates. We used benzyl-2-acetamido-2-deoxy-α-d-galactopyranoside (BAGN), a compound that has been widely used to inhibit O-glycosylation in several cell lines. Pretreatment and culture of PHA-blast target cells with BAGN increased the percentage of HIV-infected cells (7.6-fold, p = 0.0115), the per-cell amount of HIV p24 protein (1.3-fold, p = 0.2475), and the viral particles in culture supernatants (7.1-fold, p = 0.0029) compared to BAGN-free cultures. Initiating infection with virus previously grown in the presence of BAGN further increased percentage of infected cells (30-fold, p < 0.0001), intracellular p24 (1.5-fold, p = 0.0433), and secreted viral particles (74-fold, p < 0.0001). BAGN-treated target cells showed less CD25 and CCR5 expression, but increased HLA-DR surface expression, which positively correlated with the number of infected cells. Importantly, BAGN improved viral outgrowth kinetics in 66% of the samples...Continue Reading

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Citations

Oct 23, 2019·International Journal of Molecular Sciences·Felix WiedmannConstanze Schmidt
May 22, 2020·Drugs·Lucia Bailon AlvarezChristian Brander
Jan 31, 2019·Frontiers in Endocrinology·Marine FerronBenjamin Lauzier
Jan 31, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Israel Olapeju BolanleTimothy M Palmer
Feb 9, 2021·Frontiers in Immunology·Alex OlveraChristian Brander

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Methods Mentioned

BETA
glycosylation
flow cytometry
enzyme-linked immunosorbent assay
Assay
ELISA

Software Mentioned

MUSCLE
TRIMMOMATIC
MEGA5
bowtie
FlowJo
PEAR
Usearch
geno2pheno
FastTree2

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