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Hepatology. 2016 Jan;63(1):35-48. doi: 10.1002/hep.28013. Epub 2015 Oct 6.

A targeted functional RNA interference screen uncovers glypican 5 as an entry factor for hepatitis B and D viruses.

Author information

1
Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France.
2
Université de Strasbourg, Strasbourg, France.
3
IGBMC, Plateforme de Criblage Haut-débit, Illkirch, France.
4
Institut Hospitalo-Universitaire, Pôle Hépato-digestif, Nouvel Hôpital Civil, Strasbourg, France.
5
Inserm, U1052, CNRS UMR 5286, Cancer Research Center of Lyon, Université de Lyon, Lyon, France.
6
INTS, Laboratoire de Virologie Moléculaire, Paris, France.
7
Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
8
Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA.
9
Program in Translational NeuroPsychiatric Genomics, Brigham and Women's Hospital, Harvard Medical School, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA.
10
KU Leuven Technology Campus Geel, AdvISe, Geel, Belgium.
11
Department of Internal Medicine II/Molecular Biology, University Hospital Freiburg, Freiburg, Germany.

Abstract

Chronic hepatitis B and D infections are major causes of liver disease and hepatocellular carcinoma worldwide. Efficient therapeutic approaches for cure are absent. Sharing the same envelope proteins, hepatitis B virus and hepatitis delta virus use the sodium/taurocholate cotransporting polypeptide (a bile acid transporter) as a receptor to enter hepatocytes. However, the detailed mechanisms of the viral entry process are still poorly understood. Here, we established a high-throughput infectious cell culture model enabling functional genomics of hepatitis delta virus entry and infection. Using a targeted RNA interference entry screen, we identified glypican 5 as a common host cell entry factor for hepatitis B and delta viruses.

CONCLUSION:

These findings advance our understanding of virus cell entry and open new avenues for curative therapies. As glypicans have been shown to play a role in the control of cell division and growth regulation, virus-glypican 5 interactions may also play a role in the pathogenesis of virus-induced liver disease and cancer.

Comment in

PMID:
26224662
DOI:
10.1002/hep.28013
[Indexed for MEDLINE]

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