In vivo expression of a new hepatitis B virus protein encoded by a spliced RNA
In vivo expression of a new hepatitis B virus protein encoded by a spliced RNA
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DOI：
10.1172/jci8098
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发表时间：
2000-01-01
影响因子：
15.9
通讯作者：
Kremsdorf, D
中科院分区：
文献类型：
--
作者：
Soussan, P;Garreau, F;Kremsdorf, D
乙肝病毒是一种基因组结构紧凑的小DNA病毒。到目前为止，所有已鉴定的乙肝病毒蛋白都是由未剪接的乙肝病毒RNA编码的。剪接的HBVRNA已经被描述，但它们的功能尚不清楚。我们在这里展示了单个剪接的HBVRNA在体内编码脐带状HBV蛋白。这种乙肝病毒剪接产生的蛋白(HBSP)对应于病毒聚合酶的一部分和剪接事件产生的新的开放阅读框架的融合。在体内，在乙肝病毒感染的肝脏样本中发现HBSP蛋白，三分之一的慢性乙肝携带者的血清样本中存在抗HBSP抗体。在体外，HBSP的异位表达对病毒DNA的复制或转录没有影响，但在没有细胞周期阻断的情况下诱导细胞凋亡。总体而言，我们的结果表明，乙肝病毒已经进化出一种通过RNA剪接直接调节病毒与细胞相互作用的机制。
Hepatitis B virus (HBV) is a small DNA virus with a compact genomic organization. All HBV proteins identified to date have been encoded by unspliced HBV RNAs. Spliced HBV RNAs have been described, but their functions are unknown. We show here that a singly spliced HBV RNA encodes a navel HBV protein in vivo. This HBV splice-generated protein (HBSP) corresponds to the fusion of a part of the viral polymerase and a new open reading frame that is created by the splicing event. In vivo, HBSP protein was found in HBV-infected liver samples, and anti-HBSP antibodies occurred in one-third of sera samples collected from chronic HBV carriers. In vitro, the ectopic expression of HBSP had no effect on viral DNA replication or transcription but induced cell apoptosis without a cell-cycle block. Overall, our results suggest that HBV has evolved a mechanism that directly modulates virus-cell interaction through RNA splicing.