Generation of a human hepatoma cell line supporting efficient replication of a lamivudine resistant hepatitis B virus.

Abstract:

:Emergence of lamivudine (LAM) resistance causes treatment failure in patients with chronic hepatitis B and compromise the efficacy of subsequent salvage therapies with other nucleot(s)ide analogs (NAs). Establishment of cell-based assays supporting LAM-resistant hepatitis B virus (HBV) replication will not only provide tools for investigating the replication property, but also screening for antiviral agents efficiently inhibiting the replication of LAM-resistant HBV variants. Accordingly, a human hepatoma (HepG2)-derived cell line was established by stable transfection of a plasmid containing a 1.2 unit length of HBV genome harboring rtL180M and rtM204V mutations that confer LAM resistance. In addition to support efficient viral genome replication, the cell line also produces high levels of HBV virions and subviral particles. As expected, HBV DNA replication in this cell line is completely resistant to lamivudine, but sensitive to adefovir (ADV), entecavir (ETV) and tenofovir (TDF). The cell line is suitable for screening for antiviral agents that inhibit LAM-resistant HBV replication and inhibitors of HBsAg biosynthesis and secretion, which may reduce HBsAg antigenemia and ultimately help to restore host antiviral immune response against HBV and cure chronic HBV infection.

journal_name

J Virol Methods

authors

Zhang Y,Zhang Y,Kang Y,Wang J,Liu H,Zhu H,Qin Y,Mao R,Lin X,Lu M,Zhang J

doi

10.1016/j.jviromet.2014.02.008

subject

Has Abstract

pub_date

2014-06-01 00:00:00

pages

51-6

eissn

0166-0934

issn

1879-0984

pii

S0166-0934(14)00051-2

journal_volume

201

pub_type

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