Dépôt numérique

Inhibition of HBsAg secretion by nucleic acid polymers in HepG2.2.15 cells

Blanchet, Matthieu; Sinnathamby, Vigigah; Vaillant, Andrew et Labonté, Patrick ORCID logoORCID: https://orcid.org/0000-0001-7262-3125 (2019). Inhibition of HBsAg secretion by nucleic acid polymers in HepG2.2.15 cells Antiviral Research , vol. 164 . pp. 97-105. DOI: 10.1016/j.antiviral.2019.02.009.

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More than 290 million people have chronic HBV infection and are at risk of developing cirrhosis and hepatocellular carcinoma. HBV subviral particles are produced in large excess over virions in infected patients and are the primary source of HBsAg, which is postulated to be important in allowing HBV to chronically persist by interfering with immune function. Nucleic acid polymers (NAPs) have been shown to result in clearance of HBsAg from the blood in pre-clinical and clinical studies. In this study, we show for the first time the recapitulation of NAP- induced inhibition of secretion of HBsAg in vitro using the human HepG2.2.15 cell line. With the restoration of endosomal release of NAPs in vitro using the UNC7938 compound, NAPs were observed to selectively impair the secretion of HBsAg without any intracellular HBsAg accumulation. Additionally, the structure-activity relationship of NAPs for this antiviral activity is similar to that previously reported in other infectious diseases and identifies an exposed hydrophobic protein domain as the target interface for this antiviral effect. The presented in vitro model, the first one to be based on a human derived cell line that constitutively expresses HBV, is a very promising tool for the identification of the host proteins(s) targeted by NAPs.

Type de document: Article
Mots-clés libres: HBsAg; HepG2.2.15; In vitro model; Nucleic acid polymer; REP 2139
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 06 août 2019 14:25
Dernière modification: 15 févr. 2022 18:21
URI: https://espace.inrs.ca/id/eprint/8089

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