Differential regulation of hepatitis B virus core protein expression and genome replication by a small upstream open reading frame and naturally occurring mutations in the precore region.
Differential regulation of hepatitis B virus core protein expression and genome replication by a small upstream open reading frame and naturally occurring mutations in the precore region.
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小型上游开放阅读框和前核心区域自然发生的突变对乙型肝炎病毒核心蛋白表达和基因组复制的差异调节
DOI：
10.1016/j.virol.2017.02.020
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发表时间：
2017-05
期刊：
影响因子：
3.7
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Zong L;Qin Y;Jia H;Ye L;Wang Y;Zhang J;Wands JR;Tong S;Li J
B型肝炎病毒（HBV）转录两个3.5 kb RNA亚类：用于表达B e抗原（HBeAg）的前核心RNA和用于核心和P蛋白翻译以及基因组复制的前基因组RNA。前C区的突变可以阻止HBeAg的表达，而上游开放阅读框（uORF）被认为是核心蛋白翻译的负调控因子。我们采用可复制HBV DNA构建体和Huh7细胞中的瞬时转染实验来验证uORF效应并探索前C RNA的替代功能。如在一些HBV基因型中存在的uORF或额外的ATG密码子的优化的Kozak序列降低核心蛋白表达。G1896A无义突变比突变的前核心ATG更有效地促进核心蛋白表达，而+1移码突变无效。总之，各种HBeAg阴性前C区突变和影响uORF的突变差异调节核心蛋白表达和基因组复制。
Hepatitis B virus (HBV) transcribes two subsets of 3.5-kb RNAs: precore RNA for hepatitis B e antigen (HBeAg) expression, and pregenomic RNA for core and P protein translation as well as genome replication. HBeAg expression could be prevented by mutations in the precore region, while an upstream open reading frame (uORF) has been proposed as a negative regulator of core protein translation. We employed replication competent HBV DNA constructs and transient transfection experiments in Huh7 cells to verify the uORF effect and to explore the alternative function of precore RNA. Optimized Kozak sequence for the uORF or extra ATG codons as present in some HBV genotypes reduced core protein expression. G1896A nonsense mutation promoted more efficient core protein expression than mutated precore ATG, while a +1 frameshift mutation was ineffective. In conclusion, various HBeAg-negative precore mutations and mutations affecting uORF differentially regulate core protein expression and genome replication.
影响因子：
4.5
作者：
Cho SW;Shin YJ;Hahm KB;Jin JH;Kim YS;Kim JH;Kim HJ
通讯作者：
Kim HJ