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Novel Woodchuck Hepatitis Virus (WHV) Transgene Mouse Models Show Sex-Dependent WHV Replicative Activity and Development of Spontaneous Immune Responses to WHV Proteins
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| Zeitschriftentitel: | Journal of Virology |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , |
| In: | Journal of Virology, 88, 2014, 3, S. 1573-1581 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society for Microbiology
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| Schlagwörter: |
| author_facet |
Meng, Zhongji Ma, Zhiyong Zhang, Ejuan Kosinska, Anna D. Liu, Jia Zhang, Xiaoyong Zhou, Tianlun Wu, Jun Dahmen, Uta Dirsch, Olaf Yang, Dongliang Roggendorf, Michael Lu, Mengji Meng, Zhongji Ma, Zhiyong Zhang, Ejuan Kosinska, Anna D. Liu, Jia Zhang, Xiaoyong Zhou, Tianlun Wu, Jun Dahmen, Uta Dirsch, Olaf Yang, Dongliang Roggendorf, Michael Lu, Mengji |
|---|---|
| author |
Meng, Zhongji Ma, Zhiyong Zhang, Ejuan Kosinska, Anna D. Liu, Jia Zhang, Xiaoyong Zhou, Tianlun Wu, Jun Dahmen, Uta Dirsch, Olaf Yang, Dongliang Roggendorf, Michael Lu, Mengji |
| spellingShingle |
Meng, Zhongji Ma, Zhiyong Zhang, Ejuan Kosinska, Anna D. Liu, Jia Zhang, Xiaoyong Zhou, Tianlun Wu, Jun Dahmen, Uta Dirsch, Olaf Yang, Dongliang Roggendorf, Michael Lu, Mengji Journal of Virology Novel Woodchuck Hepatitis Virus (WHV) Transgene Mouse Models Show Sex-Dependent WHV Replicative Activity and Development of Spontaneous Immune Responses to WHV Proteins Virology Insect Science Immunology Microbiology |
| author_sort |
meng, zhongji |
| spelling |
Meng, Zhongji Ma, Zhiyong Zhang, Ejuan Kosinska, Anna D. Liu, Jia Zhang, Xiaoyong Zhou, Tianlun Wu, Jun Dahmen, Uta Dirsch, Olaf Yang, Dongliang Roggendorf, Michael Lu, Mengji 0022-538X 1098-5514 American Society for Microbiology Virology Insect Science Immunology Microbiology http://dx.doi.org/10.1128/jvi.02086-13 <jats:title>ABSTRACT</jats:title> <jats:p>The woodchuck model is an informative model for studies on hepadnaviral infection. In this study, woodchuck hepatitis virus (WHV) transgenic (Tg) mouse models based on C57BL/6 mice were established to study the pathogenesis associated with hepadnaviral infection. Two lineages of WHV Tg mice, harboring the WHV wild-type genome (lineage 1217) and a mutated WHV genome lacking surface antigen (lineage 1281), were generated. WHV replication intermediates were detected by Southern blotting. DNA vaccines against WHV proteins were applied by intramuscular injection. WHV-specific immune responses were analyzed by flow cytometry and enzyme-linked immunosorbent assays (ELISAs). The presence of WHV transgenes resulted in liver-specific but sex- and age-dependent WHV replication in Tg mice. Pathological changes in the liver, including hepatocellular dysplasia, were observed in aged Tg mice, suggesting that the presence of WHV transgenes may lead to liver diseases. Interestingly, Tg mice of lineage 1281 spontaneously developed T- and B-cell responses to WHV core protein (WHcAg). DNA vaccination induced specific immune responses to WHV proteins in WHV Tg mice, indicating a tolerance break. The magnitude of the induced WHcAg-specific immune responses was dependent on the effectiveness of different DNA vaccines and was associated with a decrease in WHV loads in mice. In conclusion, sex- and age-dependent viral replication, development of autoimmune responses to viral antigens, pathological changes in the liver in WHV Tg mice, and the possibility of breaking immune tolerance to WHV transgenes will allow future studies on pathogenesis related to hepadnaviral infection and therapeutic vaccines.</jats:p> Novel Woodchuck Hepatitis Virus (WHV) Transgene Mouse Models Show Sex-Dependent WHV Replicative Activity and Development of Spontaneous Immune Responses to WHV Proteins Journal of Virology |
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| title |
Novel Woodchuck Hepatitis Virus (WHV) Transgene Mouse Models Show Sex-Dependent WHV Replicative Activity and Development of Spontaneous Immune Responses to WHV Proteins |
| title_unstemmed |
Novel Woodchuck Hepatitis Virus (WHV) Transgene Mouse Models Show Sex-Dependent WHV Replicative Activity and Development of Spontaneous Immune Responses to WHV Proteins |
| title_full |
Novel Woodchuck Hepatitis Virus (WHV) Transgene Mouse Models Show Sex-Dependent WHV Replicative Activity and Development of Spontaneous Immune Responses to WHV Proteins |
| title_fullStr |
Novel Woodchuck Hepatitis Virus (WHV) Transgene Mouse Models Show Sex-Dependent WHV Replicative Activity and Development of Spontaneous Immune Responses to WHV Proteins |
| title_full_unstemmed |
Novel Woodchuck Hepatitis Virus (WHV) Transgene Mouse Models Show Sex-Dependent WHV Replicative Activity and Development of Spontaneous Immune Responses to WHV Proteins |
| title_short |
Novel Woodchuck Hepatitis Virus (WHV) Transgene Mouse Models Show Sex-Dependent WHV Replicative Activity and Development of Spontaneous Immune Responses to WHV Proteins |
| title_sort |
novel woodchuck hepatitis virus (whv) transgene mouse models show sex-dependent whv replicative activity and development of spontaneous immune responses to whv proteins |
| topic |
Virology Insect Science Immunology Microbiology |
| url |
http://dx.doi.org/10.1128/jvi.02086-13 |
| publishDate |
2014 |
| physical |
1573-1581 |
| description |
<jats:title>ABSTRACT</jats:title>
<jats:p>The woodchuck model is an informative model for studies on hepadnaviral infection. In this study, woodchuck hepatitis virus (WHV) transgenic (Tg) mouse models based on C57BL/6 mice were established to study the pathogenesis associated with hepadnaviral infection. Two lineages of WHV Tg mice, harboring the WHV wild-type genome (lineage 1217) and a mutated WHV genome lacking surface antigen (lineage 1281), were generated. WHV replication intermediates were detected by Southern blotting. DNA vaccines against WHV proteins were applied by intramuscular injection. WHV-specific immune responses were analyzed by flow cytometry and enzyme-linked immunosorbent assays (ELISAs). The presence of WHV transgenes resulted in liver-specific but sex- and age-dependent WHV replication in Tg mice. Pathological changes in the liver, including hepatocellular dysplasia, were observed in aged Tg mice, suggesting that the presence of WHV transgenes may lead to liver diseases. Interestingly, Tg mice of lineage 1281 spontaneously developed T- and B-cell responses to WHV core protein (WHcAg). DNA vaccination induced specific immune responses to WHV proteins in WHV Tg mice, indicating a tolerance break. The magnitude of the induced WHcAg-specific immune responses was dependent on the effectiveness of different DNA vaccines and was associated with a decrease in WHV loads in mice. In conclusion, sex- and age-dependent viral replication, development of autoimmune responses to viral antigens, pathological changes in the liver in WHV Tg mice, and the possibility of breaking immune tolerance to WHV transgenes will allow future studies on pathogenesis related to hepadnaviral infection and therapeutic vaccines.</jats:p> |
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| author | Meng, Zhongji, Ma, Zhiyong, Zhang, Ejuan, Kosinska, Anna D., Liu, Jia, Zhang, Xiaoyong, Zhou, Tianlun, Wu, Jun, Dahmen, Uta, Dirsch, Olaf, Yang, Dongliang, Roggendorf, Michael, Lu, Mengji |
| author_facet | Meng, Zhongji, Ma, Zhiyong, Zhang, Ejuan, Kosinska, Anna D., Liu, Jia, Zhang, Xiaoyong, Zhou, Tianlun, Wu, Jun, Dahmen, Uta, Dirsch, Olaf, Yang, Dongliang, Roggendorf, Michael, Lu, Mengji, Meng, Zhongji, Ma, Zhiyong, Zhang, Ejuan, Kosinska, Anna D., Liu, Jia, Zhang, Xiaoyong, Zhou, Tianlun, Wu, Jun, Dahmen, Uta, Dirsch, Olaf, Yang, Dongliang, Roggendorf, Michael, Lu, Mengji |
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| description | <jats:title>ABSTRACT</jats:title> <jats:p>The woodchuck model is an informative model for studies on hepadnaviral infection. In this study, woodchuck hepatitis virus (WHV) transgenic (Tg) mouse models based on C57BL/6 mice were established to study the pathogenesis associated with hepadnaviral infection. Two lineages of WHV Tg mice, harboring the WHV wild-type genome (lineage 1217) and a mutated WHV genome lacking surface antigen (lineage 1281), were generated. WHV replication intermediates were detected by Southern blotting. DNA vaccines against WHV proteins were applied by intramuscular injection. WHV-specific immune responses were analyzed by flow cytometry and enzyme-linked immunosorbent assays (ELISAs). The presence of WHV transgenes resulted in liver-specific but sex- and age-dependent WHV replication in Tg mice. Pathological changes in the liver, including hepatocellular dysplasia, were observed in aged Tg mice, suggesting that the presence of WHV transgenes may lead to liver diseases. Interestingly, Tg mice of lineage 1281 spontaneously developed T- and B-cell responses to WHV core protein (WHcAg). DNA vaccination induced specific immune responses to WHV proteins in WHV Tg mice, indicating a tolerance break. The magnitude of the induced WHcAg-specific immune responses was dependent on the effectiveness of different DNA vaccines and was associated with a decrease in WHV loads in mice. In conclusion, sex- and age-dependent viral replication, development of autoimmune responses to viral antigens, pathological changes in the liver in WHV Tg mice, and the possibility of breaking immune tolerance to WHV transgenes will allow future studies on pathogenesis related to hepadnaviral infection and therapeutic vaccines.</jats:p> |
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| spelling | Meng, Zhongji Ma, Zhiyong Zhang, Ejuan Kosinska, Anna D. Liu, Jia Zhang, Xiaoyong Zhou, Tianlun Wu, Jun Dahmen, Uta Dirsch, Olaf Yang, Dongliang Roggendorf, Michael Lu, Mengji 0022-538X 1098-5514 American Society for Microbiology Virology Insect Science Immunology Microbiology http://dx.doi.org/10.1128/jvi.02086-13 <jats:title>ABSTRACT</jats:title> <jats:p>The woodchuck model is an informative model for studies on hepadnaviral infection. In this study, woodchuck hepatitis virus (WHV) transgenic (Tg) mouse models based on C57BL/6 mice were established to study the pathogenesis associated with hepadnaviral infection. Two lineages of WHV Tg mice, harboring the WHV wild-type genome (lineage 1217) and a mutated WHV genome lacking surface antigen (lineage 1281), were generated. WHV replication intermediates were detected by Southern blotting. DNA vaccines against WHV proteins were applied by intramuscular injection. WHV-specific immune responses were analyzed by flow cytometry and enzyme-linked immunosorbent assays (ELISAs). The presence of WHV transgenes resulted in liver-specific but sex- and age-dependent WHV replication in Tg mice. Pathological changes in the liver, including hepatocellular dysplasia, were observed in aged Tg mice, suggesting that the presence of WHV transgenes may lead to liver diseases. Interestingly, Tg mice of lineage 1281 spontaneously developed T- and B-cell responses to WHV core protein (WHcAg). DNA vaccination induced specific immune responses to WHV proteins in WHV Tg mice, indicating a tolerance break. The magnitude of the induced WHcAg-specific immune responses was dependent on the effectiveness of different DNA vaccines and was associated with a decrease in WHV loads in mice. In conclusion, sex- and age-dependent viral replication, development of autoimmune responses to viral antigens, pathological changes in the liver in WHV Tg mice, and the possibility of breaking immune tolerance to WHV transgenes will allow future studies on pathogenesis related to hepadnaviral infection and therapeutic vaccines.</jats:p> Novel Woodchuck Hepatitis Virus (WHV) Transgene Mouse Models Show Sex-Dependent WHV Replicative Activity and Development of Spontaneous Immune Responses to WHV Proteins Journal of Virology |
| spellingShingle | Meng, Zhongji, Ma, Zhiyong, Zhang, Ejuan, Kosinska, Anna D., Liu, Jia, Zhang, Xiaoyong, Zhou, Tianlun, Wu, Jun, Dahmen, Uta, Dirsch, Olaf, Yang, Dongliang, Roggendorf, Michael, Lu, Mengji, Journal of Virology, Novel Woodchuck Hepatitis Virus (WHV) Transgene Mouse Models Show Sex-Dependent WHV Replicative Activity and Development of Spontaneous Immune Responses to WHV Proteins, Virology, Insect Science, Immunology, Microbiology |
| title | Novel Woodchuck Hepatitis Virus (WHV) Transgene Mouse Models Show Sex-Dependent WHV Replicative Activity and Development of Spontaneous Immune Responses to WHV Proteins |
| title_full | Novel Woodchuck Hepatitis Virus (WHV) Transgene Mouse Models Show Sex-Dependent WHV Replicative Activity and Development of Spontaneous Immune Responses to WHV Proteins |
| title_fullStr | Novel Woodchuck Hepatitis Virus (WHV) Transgene Mouse Models Show Sex-Dependent WHV Replicative Activity and Development of Spontaneous Immune Responses to WHV Proteins |
| title_full_unstemmed | Novel Woodchuck Hepatitis Virus (WHV) Transgene Mouse Models Show Sex-Dependent WHV Replicative Activity and Development of Spontaneous Immune Responses to WHV Proteins |
| title_short | Novel Woodchuck Hepatitis Virus (WHV) Transgene Mouse Models Show Sex-Dependent WHV Replicative Activity and Development of Spontaneous Immune Responses to WHV Proteins |
| title_sort | novel woodchuck hepatitis virus (whv) transgene mouse models show sex-dependent whv replicative activity and development of spontaneous immune responses to whv proteins |
| title_unstemmed | Novel Woodchuck Hepatitis Virus (WHV) Transgene Mouse Models Show Sex-Dependent WHV Replicative Activity and Development of Spontaneous Immune Responses to WHV Proteins |
| topic | Virology, Insect Science, Immunology, Microbiology |
| url | http://dx.doi.org/10.1128/jvi.02086-13 |