Effect of HBV mutants in different topological regions on the synthesis and secretion of HBsAg
- Author:
HE Pei
;
ZHANG Peixin
;
LI Yonggang
- Publication Type:Journal Article
- Keywords:
Occult hepatitis B;
HBV mutants;
HBsAg
- From:
China Tropical Medicine
2024;24(12):1519-
- CountryChina
- Language:Chinese
-
Abstract:
Objective Because occult hepatitis B virus (HBV) variants are highly transmissible and harmful, the investigation of HBsAg antigenic mutation, synthesis, and secretion will provide useful guidance for addressing clinical diagnosis and treatment of occult hepatitis B infection. Methods The HBV gene sequences of OBI patients were successfully cloned to obtain HBsAg single and multi-locus mutants. The protein similarity and stability of the wild-type and mutant structural model were analyzed using AlphaFold2.3 software, and the wild-type, single and multi-locus mutants were transfected into Huh7 cells to analyze the intra- and extracellular synthesis and secretion of different mutants. Results The single mutant loci Y100L, Y100C, and C139R showed smaller root mean squared deviation (RMSD) values compared to the wild type, while G145R had a larger RMSD value. Moreover, the Y100L mutation exhibited the smallest thermos-energetic difference (∆∆G), followed by Y100C, C139R, and G145R. The RMSD values of the three multi-locus mutants were less than 1 compared to the wild type, and the RMSD values of T63I/Y100L/Q101K were the smallest, followed by T125A/F158L/V224G and S113T/F220C. The synthesis, secretion, and secretion efficiency of Y100C, C139R, and G145R were significantly different from the wild-type (P<0.05); the intracellular synthesis and secretion efficiency of S113T/F220C were statistically different compared to the wild-type (P<0.05); the intracellular synthesis and secretion efficiency of T63I/Y100L/Q101K were statistically different compared to the wild type (P<0.05). Conclusion Some single-point mutants in the luminal region of the endoplasmic reticulum reduce the synthesis and secretion of HBsAg in hepatocytes. Certain multi-loci mutants combining the luminal region of the endoplasmic reticulum with other structural regions increase the synthesis of HBsAg in hepatocytes but reduce secretion efficiency.
- Full text:202511131524509901914.Effect of HBV mutants in different topological regions on the synthesis and secretion of HBsAg.pdf
