Inhibitory effect of HMGN2 protein on human hepatitis B virus expression and replication in the HepG2.2.15 cell line

We report the development and isolation of a cell line, termed HepAD38, that replicates human hepatitis B virus (HBV) under conditions that can be regulated with tetracycline. In the presence of the antibiotic, this cell line is free of virus due to the repression of pregenomic (pg) RNA synthesis. Upon removal of tetracycline from the culture medium, the cells express viral pg RNA, accumulate subviral particles in the cytoplasm that contain DNA intermediates characteristic of viral replication, and secrete virus-like particles into the supernatant. Since the HepAD38 cell line can produce high levels of HBV DNA, it should be useful for analyses of the viral replication cycle that depend upon viral DNA synthesis in a synchronized fashion. In addition, this cell line has been formatted into a high-throughput, cell-based assay that permits the large-scale screening of diverse compound libraries for new classes of inhibitors of HBV replication.

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Inhibitory Effect of Bovine Lactoferrin on Human Hepatitis B Virus Replication in HepG2.2.15 Cells

BIO ◽

10.5618/bio.2011.v1.n1.3 ◽

2011 ◽

Vol 1 (1) ◽

pp. 64-66

Author(s):

Jiahong Lee ◽

Yusi Zhou ◽

Mingxuan Wang ◽

Wei Ning Chen

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Virus Replication ◽

Inhibitory Effect ◽

Bovine Lactoferrin ◽

Human Hepatitis ◽

B Virus

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Replication Advantage and Host Factor-Independent Phenotypes Attributable to a Common Naturally Occurring Capsid Mutation (I97L) in Human Hepatitis B Virus

Journal of Virology ◽

10.1128/jvi.76.23.12069-12077.2002 ◽

2002 ◽

Vol 76 (23) ◽

pp. 12069-12077 ◽

Cited By ~ 26

Author(s):

Fat-Moon Suk ◽

Min-Hui Lin ◽

Margaret Newman ◽

Shann Pan ◽

Sheng-Hsuan Chen ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Cell Line ◽

Core Protein ◽

Hepatoma Cell ◽

Host Factor ◽

Wild Type ◽

Human Hepatitis ◽

Huh7 Cells ◽

B Virus

ABSTRACT Mutations of human hepatitis B virus (HBV) occur frequently within the capsid (core) protein in natural infections. The most frequent mutation of the core protein in HBV from Southeast Asia occurs at amino acid 97, changing an isoleucine (I) to a leucine (L). In our systematic study of virus-host interactions, we have examined the replication efficiency of a site-directed mutant, I97L, and its parental wild-type HBV in several different hepatoma cell lines. Interestingly, we found that this capsid variant replicated in human Huh7 hepatoma cells approximately 4.8-fold better than its parental wild-type HBV. A similar phenomenon was observed in another hepatoma cell line, J3. In addition, the level of encapsidated RNA pregenome in mutant I97L was about 5.7-fold higher than that of the wild-type HBV in Huh7 cells. Unlike Huh7 cells, no significant difference in viral DNA replication between the same I97L mutant and its parental wild-type HBV was observed in HepG2, a human hepatoblastoma cell line. This finding of a profound replication advantage for mutant I97L in Huh7 and J3 cells but not in HepG2 cells may have important implications for the emergence of this mutant in chronic HBV carriers. We speculate here that the mutation confers a host factor-independent growth advantage for the survival of HBV variants in gradually dedifferentiating hepatocytes and thus helps prolong viral persistence.

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