論文 - 詳細
| RRC ID | 57775 |
|---|---|
| 著者 | Ogura S, Tameda M, Sugimoto K, Ikejiri M, Usui M, Ito M, Takei Y. |
| タイトル | A substitution in the pre-S1 promoter region is associated with the viral regulation of hepatitis B virus. |
| ジャーナル | Virol J |
| Abstract |
BACKGROUND:Much evidence has demonstrated the influence of Hepatitis B virus (HBV) mutations on the clinical course of HBV infection. As large (L) protein plays a crucial role for viral entry, we hypothesized that mutations in the pre-S1 promoter region might affect the expression of L protein and subsequently change the biological characters of virus. METHODS:Patients infected with genotype C HBV were enrolled for analysis. HBV DNA sequences were inserted into a TA cloning vector and analyzed. To evaluate the effects of mutations in the pre-S1 promoter region, promoter activity and the expression of mRNA and L protein were analyzed using HepG2 cells. RESULTS:In total, 35 patients were enrolled and 13 patients (37.1%) had a single base substitution in the pre-S1 promoter region; the most frequent substitution was a G-to-A substitution at the 2765th base (G2765A) in the Sp1 region. The HBV viral load showed a negative correlation with the substitution ratio of the Sp1 region or G2765A (r = - 0.493 and - 0.473, respectively). Among those with a viral load ≤5.0 log IU/ml, patients with the G2765A substitution showed a significantly lower HBV viral load than those with the wild-type sequence. HepG2 cells transfected with the G2765A substitution vector showed reduced luciferase activity of the pre-S1 promoter, as well as reduced expression of pre-S1 mRNA and L protein. Furthermore, the G2765A substitution greatly reduced the L protein expression level of vector-produced virus particles. CONCLUSION:G2765A substitution in the pre-S1 promoter reduced the expression of L protein and resulted in a low viral load and less severe disease in chronic HBV infections. |
| 巻・号 | 16(1) |
| ページ | 59 |
| 公開日 | 2019-5-2 |
| DOI | 10.1186/s12985-019-1169-x |
| PII | 10.1186/s12985-019-1169-x |
| PMID | 31046787 |
| PMC | PMC6498540 |
| MeSH | Adolescent Adult Aged Aged, 80 and over Amino Acid Substitution Female Gene Expression Regulation, Viral* Hepatitis B virus / genetics* Hepatitis B, Chronic / virology Humans Male Middle Aged Point Mutation* Polymerase Chain Reaction Promoter Regions, Genetic* Viral Envelope Proteins / genetics* Viral Load Young Adult |
| IF | 2.579 |
| 引用数 | 1 |
| リソース情報 | |
| ヒト・動物細胞 | Hep G2(RCB1648) |