https://scholars.lib.ntu.edu.tw/handle/123456789/582030
標題: | Persistent hepatitis B viral replication in a FVB/N mouse model: Impact of host and viral factors | 作者: | Chen S.-H. Wu H.-L. JIA-HORNG KAO Hwang L.-H. |
公開日期: | 2012 | 卷: | 7 | 期: | 5 | 起(迄)頁: | e36984 | 來源出版物: | PLoS ONE | 摘要: | The mechanism underlying the chronicity of hepatitis B virus (HBV) infection has long been an interesting question. However, this mechanism remains unclear largely due to the lack of an animal model that can support persistent HBV replication and allow for the investigation of the relevant immune responses. In this study, we used hydrodynamic injection to introduce HBV replicon DNA into the livers of three different mouse strains: BALB/c, C57BL/6, and FVB/N. Interestingly, we found that an HBV clone persistently replicated in the livers of FVB/N mice for up to 50 weeks but was rapidly cleared from the livers of BALB/c and C57BL/6 mice. Flow cytometric analysis and quantitative reverse transcription PCR analysis of the mouse livers indicated that after DNA injection, FVB/N mice had few intrahepatic activated cytotoxic T lymphocytes (CTLs) and produced low levels of alanine aminotransferase, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and the CXCL9 and CXCL10 chemokines. These findings were in sharp contrast with those observed in BALB/c and C57BL/6 mice, reflecting a strong correlation between the degree of liver inflammation and viral clearance. Mutational analysis further demonstrated that a change of Asn-214 to Ser-214 in the HBV surface antigen rendered the persistent HBV clone clearable in FVB/N mice, which was accompanied by increased levels of activated CTL and upregulated expression of IFN-γ, CXCL9, and CXCL10 in the livers. These results indicate that the heterogeneity of the host factors and viral sequences may influence the immune responses against HBV. An inadequate activation of immune or inflammatory responses can lead to persistent HBV replication in vivo. ? 2012 Chen et al. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84861216964&doi=10.1371%2fjournal.pone.0036984&partnerID=40&md5=8d0d290bbfbd365158cea77eb61e98db https://scholars.lib.ntu.edu.tw/handle/123456789/582030 |
ISSN: | 1932-6203 | DOI: | 10.1371/journal.pone.0036984 | SDG/關鍵字: | alanine aminotransferase; CXCL9 chemokine; gamma interferon; gamma interferon inducible protein 10; hepatitis B surface antigen; tumor necrosis factor alpha; virus DNA; animal cell; animal experiment; animal model; animal tissue; article; Bagg albino mouse; C57BL 6 mouse; cell isolation; clone; controlled study; cytotoxic T lymphocyte; flow cytometry; FVB N mouse; hepatitis B; Hepatitis B virus; immunohistochemistry; liver; male; mouse; mouse strain; nonhuman; replicon; reverse transcription polymerase chain reaction; upregulation; viral clearance; virus mutation; virus replication; Alanine Transaminase; Animals; Chemokine CXCL10; Chemokine CXCL9; DNA Replication; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B virus; Host-Pathogen Interactions; Inflammation; Interferon-gamma; Liver; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; T-Lymphocytes, Cytotoxic; Tumor Necrosis Factor-alpha; Virus Replication; Animalia; Hepatitis B virus; Mus |
顯示於: | 臨床醫學研究所 |
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