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Investigating the hepatitis B virus life cycle using engineered reporter hepatitis B viruses
Author(s) -
Nishitsuji Hironori,
Harada Keisuke,
Ujino Saneyuki,
Zhang Jing,
Kohara Michinori,
Sugiyama Masaya,
Mizokami Masashi,
Shimotohno Kunitada
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13440
Subject(s) - hepatitis b virus , virology , hepatocellular carcinoma , reporter gene , viral life cycle , viral replication , hepatitis b , virus , biology , infectivity , hepatitis b virus pre beta , cirrhosis , medicine , cancer research , gene expression , gene , hepatitis b virus dna polymerase , biochemistry
Chronic infection with hepatitis B virus ( HBV ) increases the risk of developing fibrosis, cirrhosis or hepatocellular carcinoma. Current therapies are limited to type‐I interferons and/or nucleos(t)ide analogues; however, these are only partially effective. The development of novel anti‐ HBV agents for new treatment strategies has been hampered by the lack of a suitable system that allows the in vitro replication of HBV . Studies of virus infection/replication at the molecular level using wild‐type HBV are labor‐intensive and time‐consuming. To overcome these problems, we previously constructed a recombinant reporter HBV bearing the NanoLuc gene and showed its usefulness in identifying factors that affect HBV proliferation. Because this system mimics the early stage of the HBV life cycle faithfully, we conducted a quantitative analysis of HBV infectivity to several human hepatocyte cell lines as well as the effect of dimethyl sulfoxide and HBV protein X on the early stage of HBV proliferation using this system. Furthermore, we developed a system to produce a reporter HBV expressing a pol gene. These reporter HBV may provide an opportunity to enhance our understanding of the HBV life cycle and aid strategies for the development of new anti‐ HBV agents.

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