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Blocking neddylation elicits antiviral effect against hepatitis B virus replication
Karima Abounouh1,2, Mohammad Enamul Hoque Kayesh3,4, Haya Altawalah5,6
1Virology Unit, Viral Hepatitis Laboratory, Institut Pasteur du Maroc, 1 Place Louis Pasteur, Casablanca, 20360, Morocco.
Molecular Biology Reports
|October 30, 2021
Summary
Blocking neddylation, a process involving NEDD8, inhibits Hepatitis B Virus (HBV) replication. This discovery offers potential new therapeutic strategies for chronic hepatitis B.
Area of Science:
- Virology
- Molecular Biology
- Biochemistry
Background:
- Hepatitis B Virus (HBV) causes chronic liver disease globally.
- Mechanisms regulating HBV replication are not fully understood.
- Neddylation pathway's role in HBV is investigated.
Purpose of the Study:
- To investigate the role of neddylation in HBV replication.
- To determine if blocking neddylation impacts HBV production.
Main Methods:
- Used HBV-replicating cell lines (HepG2.2.15.7 and HepG2-hNTCP-30).
- Treated cells with siNEDD8 (siRNA) and MLN4924 (NEDD8-activating enzyme inhibitor).
- Measured HBV DNA, cccDNA, HBsAg, HBeAg, and HBcrAg levels.
Main Results:
- HBV infection increased NEDD8 expression in liver cells.
- NEDD8 knockdown or inhibition reduced HBV replication.
- HBsAg and HBeAg secretion decreased, while HBcrAg remained unaffected.
- Persistent cccDNA levels indicate ongoing viral presence.
Conclusions:
- Blocking the neddylation pathway shows antiviral effects against HBV.
- Neddylation pathway manipulation offers potential therapeutic strategies for chronic hepatitis B.
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