TY - JOUR
T1 - Investigating the hepatitis B virus life cycle using engineered reporter hepatitis B viruses
AU - Nishitsuji, Hironori
AU - Harada, Keisuke
AU - Ujino, Saneyuki
AU - Zhang, Jing
AU - Kohara, Michinori
AU - Sugiyama, Masaya
AU - Mizokami, Masashi
AU - Shimotohno, Kunitada
N1 - Funding Information:
Scientific Research from the Ministry of Health, Labor, and Welfare of Japan, Grant/ Award Number: H24-006; the Research Program on Hepatitis from Japan Agency for Medical Research and Development, Grant/ Award Number: 17fk0310104 h0001
Funding Information:
We thank Ms Hiromi Yamamoto and Ritsuko Shiina for technical assistance. This work was partly supported by Grants-in-Aid for Scientific Research from the Ministry of Health, Labor, and Welfare of Japan, by Grants-in-Aids for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan and by the Research Program on Hepatitis from Japan Agency for Medical Research and Development, AMED.
Publisher Copyright:
© 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
PY - 2018/1
Y1 - 2018/1
N2 - 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.
AB - 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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U2 - 10.1111/cas.13440
DO - 10.1111/cas.13440
M3 - Article
C2 - 29121422
AN - SCOPUS:85040697417
VL - 109
SP - 241
EP - 249
JO - Cancer Science
JF - Cancer Science
SN - 1347-9032
IS - 1
ER -