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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2021
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oai:doaj.org-article:936b7d4f3a05426180767516fa5fb8ee2021-11-12T04:39:17ZAmino Acid Polymorphism in Hepatitis B Virus Associated With Functional CureSummary2352-345X10.1016/j.jcmgh.2021.07.013https://doaj.org/article/936b7d4f3a05426180767516fa5fb8ee2021-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2352345X21001594https://doaj.org/toc/2352-345XBackground & 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.Takashi HondaNorie YamadaAsako MurayamaMasaaki ShiinaHussein Hassan AlyAsuka KatoTakanori ItoYoji IshizuTeiji KuzuyaMasatoshi IshigamiYoshiki MurakamiTomohisa TanakaKohji MoriishiHironori NishitsujiKunitada ShimotohnoTetsuya IshikawaMitsuhiro FujishiroMasamichi MuramatsuTakaji WakitaTakanobu KatoElsevierarticleHBccccDNAHBVccDiseases of the digestive system. GastroenterologyRC799-869ENCellular and Molecular Gastroenterology and Hepatology, Vol 12, Iss 5, Pp 1583-1598 (2021) |
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DOAJ |
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HBc cccDNA HBVcc Diseases of the digestive system. Gastroenterology RC799-869 |
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HBc cccDNA HBVcc Diseases of the digestive system. Gastroenterology RC799-869 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 |
| 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. |
| format |
article |
| 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 |
| title |
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_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_sort |
amino acid polymorphism in hepatitis b virus associated with functional curesummary |
| publisher |
Elsevier |
| publishDate |
2021 |
| url |
https://doaj.org/article/936b7d4f3a05426180767516fa5fb8ee |
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1718431242669522944 |