Hepatitis B virus entry into cells gradually revealed

Work conducted by the team led by Alessandra Carbone (Computational and Quantitative Biology), and by a team from the Centre International de Recherche en Infectiologie (CIRI: Université Lyon 1, Inserm, CNRS, ENS de Lyon) has shed new light on how the hepatitis B virus enters human cells. 

These results were published on June 30, 2021 in the journal eLife.

The entry of the hepatitis B virus (HBV) into liver cells requires the fusion of its membrane with that of the host cell. This step is triggered by cellular signals that are still unknown. Using a complementary computational and experimental approach, the researchers discovered two cellular signals: the protein enzyme "ERp57", which belongs to the family of protein disulfide isomerases (PDI), and the HBV fusion peptide.

The ERp57 enzyme would be able, by modulating the arrangement of disulfide bridges, to modify the conformation of the HBV S-glycoprotein (in the preS1 region), which would ultimately lead to the exposure of the fusion peptide. The authors showed in vitro and in vivo, in a mouse model with humanized liver, that blocking this enzyme can prevent HBV infection as well as hepatitis D virus (HDV) infection. This finding may point to a new therapeutic target to prevent the virus from entering the liver cells, the hepatocytes.

Hepatitis B virus

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Team lead by Alessandra Carbone : Analytical genomics

Pérez-Vargas, J.; Teppa, E.; Amirache, F.; Boson, B.; Pereira de Oliveira, R.; Combet, C.; Böckmann, A.; Fusil, F.; Freitas, N.; Carbone, A.; Cosset, F.-L. A Fusion Peptide in PreS1 and the Human Protein Disulfide Isomerase ERp57 Are Involved in Hepatitis B Virus Membrane Fusion Process. eLife 202110, e64507. https://doi.org/10.7554/eLife.64507.