Susceptibility of different hepatitis B virus isolates to interferon-alpha in a mouse model based on hydrodynamic injection.
Interferon alpha (IFN-α) is commonly used for the treatment of chronic hepatitis B (CHB) patients. Many factors including viral genetics may determine the outcome of IFN-α therapy. In this study, we tested whether the expression of IFN-α directly in the liver inhibits HBV gene expression and replica...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3950299?pdf=render |
| _version_ | 1811325025581531136 |
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| author | Jingjiao Song Yun Zhou Sheng Li Baoju Wang Xin Zheng Jun Wu Kathrin Gibbert Ulf Dittmer Mengji Lu Dongliang Yang |
| author_facet | Jingjiao Song Yun Zhou Sheng Li Baoju Wang Xin Zheng Jun Wu Kathrin Gibbert Ulf Dittmer Mengji Lu Dongliang Yang |
| author_sort | Jingjiao Song |
| collection | DOAJ |
| description | Interferon alpha (IFN-α) is commonly used for the treatment of chronic hepatitis B (CHB) patients. Many factors including viral genetics may determine the outcome of IFN-α therapy. In this study, we tested whether the expression of IFN-α directly in the liver inhibits HBV gene expression and replication using a HBV hydrodynamic injection (HI) mouse model. Two replication-competent clones from different HBV isolates that belonging to HBV genotype A and B based on a pAAV vector (pAAV-HBV-A and pAAV-HBV-B) were compared for their susceptibility to IFN-α. HBV clones were injected into mice either alone or in combination with a murine (m) IFN-α expression plasmid (pmIFN-α). HBsAg and HBeAg concentrations and HBV DNA levels in mice differed after injection of these two HBV clones. Co-application of pmIFN-α together with the two distinct isolates resulted in markedly different kinetics of decline of HBsAg, HBeAg, and HBV DNA levels in the mice. Immunohistochemical staining of liver sections with anti-HBc showed that mIFN-α application completely inhibited the expression of HBcAg in mice inoculated with pAAV-HBV-B, whereas the expression of HBcAg was only reduced in mice with pAAV-HBV-A. Consistently, mice injected with pAAV-HBV-B and pmIFN-α showed higher expression levels of the IFN-stimulated genes (ISGs) ISG15, OAS, PKR as well as proinflammatory cytokine IL-6 in the liver. In addition, expression levels of anti-inflammatory cytokine IL-10 was down-regulated significantly in liver of the mice injected with pAAV-HBV-B and pmIFN-α. Our data demonstrate that IFN-α exerts antiviral activity in HBV mouse model, but different HBV isolates may have diverse susceptibility to IFN-α. |
| first_indexed | 2024-04-13T14:25:47Z |
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| id | doaj.art-f93e4aa3d98a4ba6b678d8efb604ee3c |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T14:25:47Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-f93e4aa3d98a4ba6b678d8efb604ee3c2022-12-22T02:43:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0193e9097710.1371/journal.pone.0090977Susceptibility of different hepatitis B virus isolates to interferon-alpha in a mouse model based on hydrodynamic injection.Jingjiao SongYun ZhouSheng LiBaoju WangXin ZhengJun WuKathrin GibbertUlf DittmerMengji LuDongliang YangInterferon alpha (IFN-α) is commonly used for the treatment of chronic hepatitis B (CHB) patients. Many factors including viral genetics may determine the outcome of IFN-α therapy. In this study, we tested whether the expression of IFN-α directly in the liver inhibits HBV gene expression and replication using a HBV hydrodynamic injection (HI) mouse model. Two replication-competent clones from different HBV isolates that belonging to HBV genotype A and B based on a pAAV vector (pAAV-HBV-A and pAAV-HBV-B) were compared for their susceptibility to IFN-α. HBV clones were injected into mice either alone or in combination with a murine (m) IFN-α expression plasmid (pmIFN-α). HBsAg and HBeAg concentrations and HBV DNA levels in mice differed after injection of these two HBV clones. Co-application of pmIFN-α together with the two distinct isolates resulted in markedly different kinetics of decline of HBsAg, HBeAg, and HBV DNA levels in the mice. Immunohistochemical staining of liver sections with anti-HBc showed that mIFN-α application completely inhibited the expression of HBcAg in mice inoculated with pAAV-HBV-B, whereas the expression of HBcAg was only reduced in mice with pAAV-HBV-A. Consistently, mice injected with pAAV-HBV-B and pmIFN-α showed higher expression levels of the IFN-stimulated genes (ISGs) ISG15, OAS, PKR as well as proinflammatory cytokine IL-6 in the liver. In addition, expression levels of anti-inflammatory cytokine IL-10 was down-regulated significantly in liver of the mice injected with pAAV-HBV-B and pmIFN-α. Our data demonstrate that IFN-α exerts antiviral activity in HBV mouse model, but different HBV isolates may have diverse susceptibility to IFN-α.http://europepmc.org/articles/PMC3950299?pdf=render |
| spellingShingle | Jingjiao Song Yun Zhou Sheng Li Baoju Wang Xin Zheng Jun Wu Kathrin Gibbert Ulf Dittmer Mengji Lu Dongliang Yang Susceptibility of different hepatitis B virus isolates to interferon-alpha in a mouse model based on hydrodynamic injection. PLoS ONE |
| title | Susceptibility of different hepatitis B virus isolates to interferon-alpha in a mouse model based on hydrodynamic injection. |
| title_full | Susceptibility of different hepatitis B virus isolates to interferon-alpha in a mouse model based on hydrodynamic injection. |
| title_fullStr | Susceptibility of different hepatitis B virus isolates to interferon-alpha in a mouse model based on hydrodynamic injection. |
| title_full_unstemmed | Susceptibility of different hepatitis B virus isolates to interferon-alpha in a mouse model based on hydrodynamic injection. |
| title_short | Susceptibility of different hepatitis B virus isolates to interferon-alpha in a mouse model based on hydrodynamic injection. |
| title_sort | susceptibility of different hepatitis b virus isolates to interferon alpha in a mouse model based on hydrodynamic injection |
| url | http://europepmc.org/articles/PMC3950299?pdf=render |
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