A substitution in the pre-S1 promoter region is associated with the viral regulation of hepatitis B virus

Suguru Ogura, Masahiko Tameda, Kazushi Sugimoto, Makoto Ikejiri, Masanobu Usui, Masaaki Ito, Yoshiyuki Takei

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

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.

Original languageEnglish
Article number59
JournalVirology Journal
Volume16
Issue number1
DOIs
Publication statusPublished - 02-05-2019
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Virology
  • Infectious Diseases

Fingerprint

Dive into the research topics of 'A substitution in the pre-S1 promoter region is associated with the viral regulation of hepatitis B virus'. Together they form a unique fingerprint.

Cite this