Amino Acid Polymorphism in Hepatitis B Virus Associated With Functional CureSummary
Background & Aims: To provide an adequate treatment strategy for chronic hepatitis B, it is essential to know which patients are expected to have a good prognosis and which patients do not require therapeutic intervention. Previously, we identified the substitution of isoleucine to leucine a...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-01-01
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| Series: | Cellular and Molecular Gastroenterology and Hepatology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352345X21001594 |
| _version_ | 1818989375570051072 |
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| author | Takashi Honda Norie Yamada Asako Murayama Masaaki Shiina Hussein Hassan Aly Asuka Kato Takanori Ito Yoji Ishizu Teiji Kuzuya Masatoshi Ishigami Yoshiki Murakami Tomohisa Tanaka Kohji Moriishi Hironori Nishitsuji Kunitada Shimotohno Tetsuya Ishikawa Mitsuhiro Fujishiro Masamichi Muramatsu Takaji Wakita Takanobu Kato |
| author_facet | Takashi Honda Norie Yamada Asako Murayama Masaaki Shiina Hussein Hassan Aly Asuka Kato Takanori Ito Yoji Ishizu Teiji Kuzuya Masatoshi Ishigami Yoshiki Murakami Tomohisa Tanaka Kohji Moriishi Hironori Nishitsuji Kunitada Shimotohno Tetsuya Ishikawa Mitsuhiro Fujishiro Masamichi Muramatsu Takaji Wakita Takanobu Kato |
| author_sort | Takashi Honda |
| collection | DOAJ |
| description | Background & Aims: To provide an adequate treatment strategy for chronic hepatitis B, it is essential to know which patients are expected to have a good prognosis and which patients do not require therapeutic intervention. Previously, we identified the substitution of isoleucine to leucine at amino acid 97 (I97L) in the hepatitis B core region as a key predictor among patients with stable hepatitis. In this study, we attempted to identify the point at which I97L affects the hepatitis B virus (HBV) life cycle and to elucidate the underlying mechanisms governing the stabilization of hepatitis. Methods: To confirm the clinical features of I97L, we used a cohort of hepatitis B e antigen–negative patients with chronic hepatitis B infected with HBV-I97 wild-type (wt) or HBV-I97L. The effects of I97L on viral characteristics were evaluated by in vitro HBV production and infection systems with the HBV reporter virus and cell culture-generated HBV. Results: The ratios of reduction in hepatitis B surface antigen and HBV DNA were higher in patients with HBV-I97L than in those with HBV-I97wt. HBV-I97L exhibited lower infectivity than HBV-I97wt in both infection systems with reporter HBV and cell culture-generated HBV. HBV-I97L virions exhibiting low infectivity primarily contained a single-stranded HBV genome. The lower efficiency of cccDNA synthesis was demonstrated after infection of HBV-I97L or transfection of the molecular clone of HBV-I97L. Conclusions: The I97L substitution reduces the level of cccDNA through the generation of immature virions with single-stranded genomes. This I97L-associated low efficiency of cccDNA synthesis may be involved in the stabilization of hepatitis. |
| first_indexed | 2024-12-20T19:37:29Z |
| format | Article |
| id | doaj.art-936b7d4f3a05426180767516fa5fb8ee |
| institution | Directory Open Access Journal |
| issn | 2352-345X |
| language | English |
| last_indexed | 2024-12-20T19:37:29Z |
| publishDate | 2021-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cellular and Molecular Gastroenterology and Hepatology |
| spelling | doaj.art-936b7d4f3a05426180767516fa5fb8ee2022-12-21T19:28:37ZengElsevierCellular and Molecular Gastroenterology and Hepatology2352-345X2021-01-0112515831598Amino Acid Polymorphism in Hepatitis B Virus Associated With Functional CureSummaryTakashi Honda0Norie Yamada1Asako Murayama2Masaaki Shiina3Hussein Hassan Aly4Asuka Kato5Takanori Ito6Yoji Ishizu7Teiji Kuzuya8Masatoshi Ishigami9Yoshiki Murakami10Tomohisa Tanaka11Kohji Moriishi12Hironori Nishitsuji13Kunitada Shimotohno14Tetsuya Ishikawa15Mitsuhiro Fujishiro16Masamichi Muramatsu17Takaji Wakita18Takanobu Kato19Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, NagoyaDepartment of Virology II, National Institute of Infectious Diseases, TokyoDepartment of Virology II, National Institute of Infectious Diseases, TokyoDepartment of Virology II, National Institute of Infectious Diseases, TokyoDepartment of Virology II, National Institute of Infectious Diseases, TokyoDepartment of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, NagoyaDepartment of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, NagoyaDepartment of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, NagoyaDepartment of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, NagoyaDepartment of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, NagoyaDepartment of Molecular Pathology, Tokyo Medical University, TokyoDepartment of Microbiology, Graduate School of Medicine, University of Yamanashi, YamanashiDepartment of Microbiology, Graduate School of Medicine, University of Yamanashi, YamanashiGenome Medical Sciences Project, National Center for Global Health and Medicine, Ichikawa, JapanGenome Medical Sciences Project, National Center for Global Health and Medicine, Ichikawa, JapanDepartment of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, NagoyaDepartment of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, NagoyaDepartment of Virology II, National Institute of Infectious Diseases, TokyoDepartment of Virology II, National Institute of Infectious Diseases, TokyoDepartment of Virology II, National Institute of Infectious Diseases, Tokyo; Correspondence Address correspondence to: Takanobu Kato, MD, PhD, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan. fax: +81-3-5285-1161.Background & Aims: To provide an adequate treatment strategy for chronic hepatitis B, it is essential to know which patients are expected to have a good prognosis and which patients do not require therapeutic intervention. Previously, we identified the substitution of isoleucine to leucine at amino acid 97 (I97L) in the hepatitis B core region as a key predictor among patients with stable hepatitis. In this study, we attempted to identify the point at which I97L affects the hepatitis B virus (HBV) life cycle and to elucidate the underlying mechanisms governing the stabilization of hepatitis. Methods: To confirm the clinical features of I97L, we used a cohort of hepatitis B e antigen–negative patients with chronic hepatitis B infected with HBV-I97 wild-type (wt) or HBV-I97L. The effects of I97L on viral characteristics were evaluated by in vitro HBV production and infection systems with the HBV reporter virus and cell culture-generated HBV. Results: The ratios of reduction in hepatitis B surface antigen and HBV DNA were higher in patients with HBV-I97L than in those with HBV-I97wt. HBV-I97L exhibited lower infectivity than HBV-I97wt in both infection systems with reporter HBV and cell culture-generated HBV. HBV-I97L virions exhibiting low infectivity primarily contained a single-stranded HBV genome. The lower efficiency of cccDNA synthesis was demonstrated after infection of HBV-I97L or transfection of the molecular clone of HBV-I97L. Conclusions: The I97L substitution reduces the level of cccDNA through the generation of immature virions with single-stranded genomes. This I97L-associated low efficiency of cccDNA synthesis may be involved in the stabilization of hepatitis.http://www.sciencedirect.com/science/article/pii/S2352345X21001594HBccccDNAHBVcc |
| spellingShingle | Takashi Honda Norie Yamada Asako Murayama Masaaki Shiina Hussein Hassan Aly Asuka Kato Takanori Ito Yoji Ishizu Teiji Kuzuya Masatoshi Ishigami Yoshiki Murakami Tomohisa Tanaka Kohji Moriishi Hironori Nishitsuji Kunitada Shimotohno Tetsuya Ishikawa Mitsuhiro Fujishiro Masamichi Muramatsu Takaji Wakita Takanobu Kato Amino Acid Polymorphism in Hepatitis B Virus Associated With Functional CureSummary Cellular and Molecular Gastroenterology and Hepatology HBc cccDNA HBVcc |
| title | Amino Acid Polymorphism in Hepatitis B Virus Associated With Functional CureSummary |
| title_full | Amino Acid Polymorphism in Hepatitis B Virus Associated With Functional CureSummary |
| title_fullStr | Amino Acid Polymorphism in Hepatitis B Virus Associated With Functional CureSummary |
| title_full_unstemmed | Amino Acid Polymorphism in Hepatitis B Virus Associated With Functional CureSummary |
| title_short | Amino Acid Polymorphism in Hepatitis B Virus Associated With Functional CureSummary |
| title_sort | amino acid polymorphism in hepatitis b virus associated with functional curesummary |
| topic | HBc cccDNA HBVcc |
| url | http://www.sciencedirect.com/science/article/pii/S2352345X21001594 |
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