論文 - 詳細
| RRC ID | 37774 |
|---|---|
| 著者 | Abe H, Ochi H, Maekawa T, Hatakeyama T, Tsuge M, Kitamura S, Kimura T, Miki D, Mitsui F, Hiraga N, Imamura M, Fujimoto Y, Takahashi S, Nakamura Y, Kumada H, Chayama K. |
| タイトル | Effects of structural variations of APOBEC3A and APOBEC3B genes in chronic hepatitis B virus infection. |
| ジャーナル | Hepatol Res |
| Abstract |
AIM:Human APOBEC3 deaminases induce G to A hypermutation in nascent DNA strand of hepatitis B virus (HBV) genomes and seem to operate as part of the innate antiviral immune system. We analyzed the importance of APOBEC3A (A3A) and APOBEC3B (A3B) proteins, which are potent inhibitors of adeno-associated-virus and long terminal repeat (LTR)-retrotransposons, in chronic HBV infection. METHODS:We focused on the common deletion polymorphism that spans from the 3' part of A3A gene to the 3' portion of A3B gene. An association study was carried out in 724 HBV carriers and 469 healthy control subjects. We also analyzed hypermutated genomes detected in deletion and insertion (non-deletion) homozygous patients to determine the effect of APOBEC3 gene deletion. Further, we performed functional analysis of A3A gene by transient transfection experiments. RESULTS:The association study showed no significant association between deletion polymorphism and chronic HBV carrier state. Context analysis also showed a negligible effect for the deletion. Rather, mild liver fibrosis was associated with APOBEC gene deletion homozygosity, suggesting that A3B deletion is not responsible for chronic HBV infection. Functional analysis of A3A showed that overexpression of A3A induced hypermutation in HBV genome, although the levels of hypermutants were less than those introduced by A3G. However, overexpression of A3A did not decrease replicative intermediates of HBV. CONCLUSION:These results suggest that A3A and A3B play little role in HBV elimination through anti-viral defense mechanisms. The significance of hypermutation induced by A3A should be investigated further. |
| 巻・号 | 39(12) |
| ページ | 1159-68 |
| 公開日 | 2009-12-1 |
| DOI | 10.1111/j.1872-034X.2009.00566.x |
| PII | HEP566 |
| PMID | 19788695 |
| IF | 3.165 |
| 引用数 | 21 |
| WOS 分野 | GASTROENTEROLOGY & HEPATOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | Hep G2(RCB1648) |