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A substitution in the pre-S1 promoter region is associated with the viral regulation of hepatitis B virus.
- Source :
-
Virology journal [Virol J] 2019 May 02; Vol. 16 (1), pp. 59. Date of Electronic Publication: 2019 May 02. - Publication Year :
- 2019
-
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.<br />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.<br />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.<br />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.
- Subjects :
- Adolescent
Adult
Aged
Aged, 80 and over
Amino Acid Substitution
Female
Hepatitis B, Chronic virology
Humans
Male
Middle Aged
Polymerase Chain Reaction
Viral Load
Young Adult
Gene Expression Regulation, Viral
Hepatitis B virus genetics
Point Mutation
Promoter Regions, Genetic
Viral Envelope Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1743-422X
- Volume :
- 16
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Virology journal
- Publication Type :
- Academic Journal
- Accession number :
- 31046787
- Full Text :
- https://doi.org/10.1186/s12985-019-1169-x