Benzyl-2-acetamido-2-deoxy-α-d-galactopyranoside increases human immunodeficiency virus replication and viral outgrowth efficacy in vitro

Olvera, Alex; Martínez, Javier P.; Casadellà, Maria; Llano, Anuska; Rosás, Míriam; Mothe, Beatriz; Ruiz Riol, Marta; Arsequell, Gemma; Valencia, Gregorio; Noguera Julián, Marc; Paredes, Roger; Meyerhans, Andreas; Brander, Christian

Benzyl-2-acetamido-2-deoxy-α-d-galactopyranoside increases human immunodeficiency virus replication and viral outgrowth efficacy in vitro

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dc.contributor.author Olvera, Alexca
dc.contributor.author Martínez, Javier P.ca
dc.contributor.author Casadellà, Mariaca
dc.contributor.author Llano, Anuskaca
dc.contributor.author Rosás, Míriamca
dc.contributor.author Mothe, Beatrizca
dc.contributor.author Ruiz Riol, Martaca
dc.contributor.author Arsequell, Gemmaca
dc.contributor.author Valencia, Gregorioca
dc.contributor.author Noguera Julián, Marcca
dc.contributor.author Paredes, Rogerca
dc.contributor.author Meyerhans, Andreasca
dc.contributor.author Brander, Christianca
dc.date.accessioned 2018-04-16T07:30:14Z
dc.date.available 2018-04-16T07:30:14Z
dc.date.issued 2018
dc.description.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 tested, including samples from HIV controllers and subjects in whom no virus could be expanded in the absence of BAGN. Sequencing of the isolated virus indicated no skewing of viral quasi-species populations when compared to BAGN-free culture conditions. BAGN also increased virus production in the ACH2 latency model when used together with latency-reversing agents. Taken together, our results identify BAGN treatment as a simple strategy to improve viral outgrowth in vitro and may provide novel insights into host restriction mechanisms and O-glycosylation-related therapeutic targets for HIV control strategies.
dc.description.sponsorship The present study was supported by grant PI12/00529 (AO) from the Instituto de Salud Carlos III, co-financed by the Fondo Europeo de Desarrollo Regional (FEDER) “Una manera de hacer Europa” and funding from the European Union's Horizon 2020 research and innovation program under grant European AIDS Vaccine Initiative 2020 (EAVI2020) #GA681137 (CB). JM and AM were supported by a grant from the Spanish Ministry of Economy, Industry and Competitiveness and FEDER grant no. SAF2016-75505-R (AEI/MINEICO/FEDER, UE). CB and AM are senior ICREA research professors. The HIVACAT program, Foundation Dormeur, Vaduz (Liechtenstein), and an unrestricted gift by Rafael Punter, Barcelona (Spain) and the Gala SIDA 2014-2016, further supported the work.
dc.format.mimetype application/pdf
dc.identifier.citation Olvera A, Martinez JP, Casadellà M, Llano A, Rosás M, Mothe B et al. Benzyl-2-Acetamido-2-Deoxy-alpha-d-Galactopyranoside Increases Human Immunodeficiency Virus Replication and Viral Outgrowth Efficacy In Vitro. Front Immunol. 2018 Jan 26;8:2010. DOI: 10.3389/fimmu.2017.02010
dc.identifier.doi http://dx.doi.org/10.3389/fimmu.2017.02010
dc.identifier.issn 1664-3224
dc.identifier.uri http://hdl.handle.net/10230/34356
dc.language.iso eng
dc.publisher Frontiersca
dc.relation.ispartof Frontiers in Immunology. 2018 Jan 26;8:2010
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/681137
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-75505-R
dc.rights © 2018 Olvera, Martinez, Casadellà, Llano, Rosás, Mothe, Ruiz-Riol, Arsequell, Valencia, Noguera-Julian, Paredes, Meyerhans and Brander. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.keyword O-glycosylation
dc.subject.keyword Benzyl-2-acetamido-2-deoxy-α-d-galactopyranoside
dc.subject.keyword Human immunodeficiency virus-1
dc.subject.keyword Infectivity
dc.subject.keyword Replication
dc.subject.keyword Viral outgrowth
dc.title Benzyl-2-acetamido-2-deoxy-α-d-galactopyranoside increases human immunodeficiency virus replication and viral outgrowth efficacy in vitroca
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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