English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/176967
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Title

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

AuthorsOlvera, Àlex; Arsequell, Gemma ; Valencia Parera, Gregorio; Brander, Christian
KeywordsHIV
HIV-1
Benzyl-2-acetamido-2-deoxy-a-d-galactopyranoside
Replication
Human immunodeficiency virus-1
O-glycosylation
Infectivity
Viral outgrowth
Issue Date26-Jan-2018
PublisherFrontiers Media
CitationFrontiers in Immunology 8 (JAN): 2010 (2018)
AbstractGlycosylation 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-a-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. © 2018 Olvera, Martinez, Casadellà, Llano, Rosás, Mothe, Ruiz-Riol, Arsequell, Valencia, Noguera-Julian, Paredes, Meyerhans and Brander.
Publisher version (URL)https://doi.org/10.3389/fimmu.2017.02010
URIhttp://hdl.handle.net/10261/176967
DOI10.3389/fimmu.2017.02010
Appears in Collections:(IQAC) Artículos
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.