Khabir, Marwa; Aliche, Asma Zahra; Sureau, Camille; Blanchet, Matthieu et Labonté, Patrick 
ORCID: https://orcid.org/0000-0001-7262-3125
(2020).
HDV alters the autophagy process to promote its genome replication
Journal of Virology
, vol. 94
, nº 4.
pp. 1-16.
DOI: 10.1128/JVI.01936-19.
Résumé
A substantial number of viruses have been demonstrated to subvert autophagy to promote their own replication. Recent publications have reported the proviral effect of autophagy induction on hepatitis B virus (HBV) replication. The hepatitis delta virus (HDV) is a defective virus and an occasional obligate satellite of HBV. However, no previous work has studied the relationship between autophagy and HDV. In this article, we analyze the impact of HBV and HDV replication on autophagy as well as the involvement of the autophagy machinery in HDV lifecycle when produced alone and in combination with HBV. We prove that HBxAg and HBsAg can induce early steps of autophagy but ultimately block the flux. It is worth noting that, the two isoforms of the HDV protein, S-HDAg and L-HDAg, can also efficiently promote autophagosome accumulation and disturb the autophagic flux. Using the CRISPR-Cas9 technology to generate specific knockouts, we demonstrate that the autophagy machinery, specifically the proteins implicated in the elongation step (ATG7, ATG5 and LC3), are important for the release of HBV without affecting the level of intracellular HBV genome. Surprisingly, the knockout of ATG5 and ATG7 decreased the intracellular HDV RNA level in both Huh7 and HepG2.2.15 cells without additional effect on HDV secretion. Therefore, we conclude that HBV and HDV have evolved to utilize the autophagy machinery so as to assist at different steps of their lifecycle.IMPORTANCE Hepatitis delta virus is a defective RNA virus that requires hepatitis B virus envelope proteins (HBsAg) to fulfill its lifecycle. Thus, HDV virus can only infect individuals at the same time as HBV (coinfection) or superinfect individuals who are already chronic carriers of HBV. The presence of HDV in the liver accelerates the progression of infection to fibrosis and to hepatic cancer. Since the current treatments against HBV are ineffective against HDV, it is of paramount importance to study the interaction between HBV, HDV and the host factors. This will help unravel new targets whereby a therapy that is capable of simultaneously impeding both viruses could be developed. In this research paper we evidence that the autophagy machinery promotes the replication of HBV and HDV at different steps of their lifecycle. Notwithstanding their contribution to HBV release, autophagy proteins seem to assist HDV intracellular replication but not its secretion.
| Type de document: | Article |
|---|---|
| Informations complémentaires: | document e01936-19 |
| Mots-clés libres: | ATG5; autophagy; chronic infection; hepatitis B virus (HBV); hepatitis delta virus (HDV); viral replication. |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 20 juill. 2021 21:26 |
| Dernière modification: | 15 févr. 2022 18:22 |
| URI: | https://espace.inrs.ca/id/eprint/11610 |
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