Long-term hepatitis B infection in a scalable hepatic co-culture system.

Abstract:

:Hepatitis B virus causes chronic infections in 250 million people worldwide. Chronic hepatitis B virus carriers are at risk of developing fibrosis, cirrhosis, and hepatocellular carcinoma. A prophylactic vaccine exists and currently available antivirals can suppress but rarely cure chronic infections. The study of hepatitis B virus and development of curative antivirals are hampered by a scarcity of models that mimic infection in a physiologically relevant, cellular context. Here, we show that cell-culture and patient-derived hepatitis B virus can establish persistent infection for over 30 days in a self-assembling, primary hepatocyte co-culture system. Importantly, infection can be established without antiviral immune suppression, and susceptibility is not donor dependent. The platform is scalable to microwell formats, and we provide proof-of-concept for its use in testing entry inhibitors and antiviral compounds.The lack of models that mimic hepatitis B virus (HBV) infection in a physiologically relevant context has hampered drug development. Here, Winer et al. establish a self-assembling, primary hepatocyte co-culture system that can be infected with patient-derived HBV without further modifications.

journal_name

Nat Commun

journal_title

Nature communications

authors

Winer BY,Huang TS,Pludwinski E,Heller B,Wojcik F,Lipkowitz GE,Parekh A,Cho C,Shrirao A,Muir TW,Novik E,Ploss A

doi

10.1038/s41467-017-00200-8

subject

Has Abstract

pub_date

2017-07-25 00:00:00

pages

125

issue

1

issn

2041-1723

pii

10.1038/s41467-017-00200-8

journal_volume

8

pub_type

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