病毒粒子相关乙型肝炎病毒基因组中分歧的前序列和来自HBV e

StephenW

Divergent preS sequences in virion associated hepatitis B virus genomes and subviral HBV surface antigen particles from HBV e antigen negative patients
Kai-Henrik Peiffer Lisa Kuhnhenn Bingfu Jiang Antonia Mondorf Johannes Vermehren Viola Knop Simone Susser Dirk Walter Julia Dietz Gert Carra ... Show more
The Journal of Infectious Diseases, jiy119, https://doi.org/10.1093/infdis/jiy119
Published:
08 March 2018

Abstract
Background

The hepatitis B virus (HBV) surface proteins (HBsAg) coat the viral particle and form subviral particles (SVPs). Loss of HBsAg represents a functional cure and is an important treatment goal.
Methods

We analyzed the impact of the HBV genotypes A-E and pre-S mutations on SVP expression in HBeAg negative chronic HBV infected patients. A HBV genome harboring a preS1-deletion was analyzed in hepatoma cells.
Results

We observed a genotype-specific ratio of the three surface proteins (SHBs/MHBs/LHBs), which reflects differences in the morphology and composition of SVPs. Deletions/mutations in the preS1/preS2 domain, detected in released viral genomes, did not affect the molecular weight of MHBs and LHBs in these patients. In contrast, LHBs molecular weight was altered in vitro using a HBV genome harboring a preS1-deletion derived from one of these patients.
Conclusion

Differences in composition of SVPs may result in a genotype-specific immunogenicity and pathogenesis. In the analyzed patients with preS-mutations secreted HBsAg and released viral genomes cannot be derived from the same genetic source. As viral genomes are derived from cccDNA, HBsAg is presumably derived from the integrated DNA. This important HBsAg source has to be considered for novel antiviral strategies in HBeAg negative chronic HBV infected patients.

StephenW

病毒粒子相关乙型肝炎病毒基因组中分歧的前序列和来自HBV e抗原阴性患者的亚病毒表面抗原颗粒
Kai-Henrik Peiffer Lisa Kuhnhenn Bingfu Jiang Antonia Mondorf Johannes Vermehren Viola Knop Simone Susser Dirk Walter Julia Dietz Gert Carra ...显示更多
“传染病杂志”，jiy119，https://doi.org/10.1093/infdis/jiy119
发布时间：
2018年3月08日

抽象
背景

乙型肝炎病毒（HBV）表面蛋白（HBsAg）包裹病毒颗粒并形成亚病毒颗粒（SVP）。 HBsAg的丢失代表功能性治愈，是一个重要的治疗目标。
方法

我们分析了HBV基因型A-E和pre-S突变对HBeAg阴性慢性HBV感染患者SVP表达的影响。在肝癌细胞中分析携带preS1缺失的HBV基因组。
结果

我们观察到三种表面蛋白（SHBs / MHBs / LHBs）的基因型特异性比率，这反映了SVP的形态和组成方面的差异。在释放的病毒基因组中检测到的preS1 / preS2结构域中的缺失/突变不影响这些患者中MHB和LHB的分子量。相比之下，LHBs分子量在体外使用携带来自这些患者之一的preS1缺失的HBV基因组而改变。
结论

SVPs组成的差异可能导致基因型特异性免疫原性和发病机理。在分析的preS-突变分泌的HBsAg患者中，所释放的病毒基因组不能从相同的遗传来源获得。由于病毒基因组来自cccDNA，所以HBsAg大概来源于整合的DNA。在HBeAg阴性慢性HBV感染患者中，必须考虑这种重要的HBsAg来源用于新型抗病毒策略。