Benzyl-2-Acetamido-2-Deoxy-α--Galactopyranoside Increases Human Immunodeficiency Virus Replication and Viral Outgrowth Efficacy In Vitro
Olvera, Alex (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Martinez, Javier P. (Universitat Pompeu Fabra. Departament de Ciències Experimentals i de la Salut)
Casadellà, Maria (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Llano Montero, Anuska (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Rosás, Míriam (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Mothe, Beatriz (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Ruiz-Riol, Marta (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Arsequell, Gemma (Institut de Química Avançada de Catalunya)
Valencia, Gregorio (Institut de Química Avançada de Catalunya)
Noguera-Julian, Marc (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Paredes, Roger (Universitat Autònoma de Barcelona. Departament de Medicina)
Meyerhans, Andreas (Institució Catalana de Recerca i Estudis Avançats)
Brander, Christian (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)

Date:	2018
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--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.
Grants:	Ministerio de Economía y Competitividad PI12/00529 European Commission 681137 Ministerio de Economía y Competitividad SAF2016-75505-R
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Human immunodeficiency virus-1 ; Benzyl-2-acetamido-2-deoxy-α--galactopyranoside ; O-glycosylation ; Viral outgrowth ; Replication ; Infectivity
Published in:	Frontiers in immunology, Vol. 8 (january 2018) , ISSN 1664-3224

DOI: 10.3389/fimmu.2017.02010
PMID: 29472913

12 p, 2.3 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Research articles
Articles > Published articles