A SIGNAL PEPTIDE ENCODED WITHIN THE PRECORE REGION OF HEPATITIS-B VIRUS DIRECTS THE SECRETION OF A HETEROGENEOUS POPULATION OF E-ANTIGENS IN XENOPUS OOCYTES
A SIGNAL PEPTIDE ENCODED WITHIN THE PRECORE REGION OF HEPATITIS-B VIRUS DIRECTS THE SECRETION OF A HETEROGENEOUS POPULATION OF E-ANTIGENS IN XENOPUS OOCYTES
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DOI：
10.1073/pnas.85.22.8405
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发表时间：
1988-11-01
影响因子：
11.1
通讯作者：
RUTTER, WJ
中科院分区：
文献类型：
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作者：
STANDRING, DN;OU, JH;RUTTER, WJ
利用人工合成的乙肝病毒(乙肝病毒)mRNAs，我们发现在非洲爪哇卵母细胞中表达的乙肝病毒核心抗原基因序列导致21 kDa胞浆核心蛋白(P21)的稳定积累。相反，前C+核心序列的表达主要导致分泌一组大小从15 kDa到22 kDa的异质性蛋白质，这些蛋白质共同显示病毒e抗原(HBeAg)的活性。我们证明，前核心区包含一个可切割的19个氨基酸的信号肽，它针对前核心区蛋白的分泌途径。易位的最初产物(P22)在迁移过程中通过分泌途径进一步加工，显然是通过富含精氨酸的羧基末端的一系列切割事件，产生多个15-18 kDa的蛋白质(P15-P18)，这些蛋白质与一些P22一起分泌。我们的结果表明，血清HBeAg是由依赖于前C区序列的信号肽介导的分泌事件产生的。
Using synthetic hepatitis B virus (HBV) mRNAs, we have shown that expression of HBV core-antigen gene sequences in Xenopus oocytes leads to the stable accumulation of 21-kDa cytoplasmic core protein (P21). In contrast, expression of precore plus core sequences leads mainly to the secretion of a heterogeneous populaton of proteins ranging in size from 15 to 22 kDa that collectively display viral e antigen (HBeAg) activity. We demonstrate that the precore region contains a cleavable 19 amino acid signal peptide that targets the precore proteins to the secretory pathway. The initial product of translocation (P22) is further processed during migration through secretory pathway, apparently by a series of cleavage events at the arginine-rich carboxyl terminus, to yield multiple proteins of 15-18kDa (P15-P18) that are secreted along with some P22. Our results indicate that serum HBeAg is generated by a signal peptide-mediated secretion event dependent on precore sequences.