The role of hepatitis B virus surface proteins in regulating the maturation and secretion of complete and incomplete virions
The role of hepatitis B virus surface proteins in regulating the maturation and secretion of complete and incomplete virions
复制标题
乙型肝炎病毒表面蛋白在调节完整和不完整病毒体成熟和分泌中的作用
DOI：
10.1099/jgv.0.001733
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发表时间：
2022
影响因子：
3.8
通讯作者：
Xiaonan Zhang
中科院分区：
文献类型：
--
作者：
Mingzhu Xu;Chang Li;Jiahui Ding;Min Wu;Yijie Tang;Zhenghong Yuan;Xiaonan Zhang
各种形式的乙肝病毒表面蛋白的表达调节成熟病毒粒子的释放，但它们是否影响其他不完整病毒粒子的释放，如裸露衣壳，目前尚不清楚。在这里，通过在HepAD38细胞中稳定过表达大或中/小型乙肝表面蛋白(LHBs，M/SHBs)，我们评估了它们对完整和不完整病毒颗粒释放的影响。LHBs的过量生产抑制了所有表面蛋白的释放，从而增加了裸露衣壳/病毒粒子的比率。这一效应伴随着细胞外HBVRNA的升高。另一方面，M/SHBs的过表达极大地促进了包膜病毒和亚病毒颗粒的分泌。病毒DNA和LHBs的原位观察显示，当LHBs过表达时，成熟的病毒粒子保留在细胞内。这些结果表明，有包膜或无包膜的病毒颗粒分泌的分子决定受细胞内大、中、小表面抗原比例的调节。这一机制可能与乙肝病毒所致慢性肝病的进展和缓解有关。
The expression of various forms of hepatitis B virus (HBV) surface proteins regulates the release of mature virion, but whether they affect the release of other incomplete viral particles, such as naked capsid, is not clear. Here, by stable overexpression of large or middle/small hepatitis B surface proteins (LHBs, M/SHBs) in HepAD38 cells, we evaluated their effects on the release of complete and incomplete viral particles. Overproduction of LHBs inhibited the release of all surface proteins, which increased the ratio of naked capsids/virions. This effect was accompanied by the elevated extracellular HBV RNA. On the other hand, overexpression of M/SHBs greatly improved the secretion of enveloped viral and subviral particles. In situ visualization of viral DNA and LHBs revealed intracellular retention of mature virions when LHBs were overexpressed. These results indicate that the molecular decision on secretion of enveloped or unenveloped viral particles is modulated by the intracellular ratio of large, middle and small surface antigens. This mechanism may be relevant in the progression and resolution of HBV-induced chronic liver disease.