A posttranscriptional regulator of Kaposi's sarcoma-associated herpesvirus interacts with RNA-binding protein PCBP1 and controls gene expression through the IRES.
A posttranscriptional regulator of Kaposi's sarcoma-associated herpesvirus interacts with RNA-binding protein PCBP1 and controls gene expression through the IRES.
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DOI：
10.1016/j.virol.2004.04.041
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发表时间：
2004-08
期刊：
影响因子：
3.7
通讯作者：
K. Nishimura;K. Ueda;Edhi Guwanan;S. Sakakibara;E. Do;E. Osaki;Kaori Yada;T. Okuno;K. Yamanishi
中科院分区：
文献类型：
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作者：
K. Nishimura;K. Ueda;Edhi Guwanan;S. Sakakibara;E. Do;E. Osaki;Kaori Yada;T. Okuno;K. Yamanishi
卡波西肉瘤相关疱疹病毒（KSHV;也称为人类疱疹病毒8，HHV-8）属于γ-疱疹病毒亚科。KSHV ORF 57基因被认为是疱疹病毒家族中保守的转录后调节因子的同源物，并且对于复制是必需的。我们产生了针对ORF 57蛋白的特异性单克隆抗体（mAb），该抗体检测KSHV感染细胞核中表达的51-kDa蛋白。我们还发现ORF 57蛋白与多聚（rC）结合蛋白1（PCBP 1）相互作用，PCBP 1是一种细胞RNA结合的转录后调节因子。ORF 57与PCBP 1的相互作用不仅增强脊髓灰质炎病毒内部核糖体进入位点（IRES）依赖性翻译的活性，而且增强X连锁凋亡抑制因子（XIAP）和KSHV vFLIP IRES的活性。实际上，当KSHV感染细胞中的复制和转录激活因子（RTA）的表达诱导ORF 57表达时，XIAP的表达增强。这些结果表明，ORF 57结合PCBP 1作为转录后调控的功能伴侣，并参与通过IRES的细胞和病毒基因的表达的调节。
Kaposi's sarcoma-associated herpesvirus (KSHV; also known as human herpesvirus 8, HHV-8) belongs to the γ-herpesvirus subfamily. The KSHV ORF57 gene is thought to be a homolog of posttranscriptional regulators that are conserved in the herpesvirus family and are essential for replication. We generated specific monoclonal antibodies (mAbs) against the ORF57 protein that detected the 51-kDa protein expressed in the nucleus of KSHV-infected cells. We also found that the ORF57 protein interacted with poly(rC)-binding protein 1 (PCBP1), a cellular RNA-binding, posttranscriptional regulator. ORF57's interaction with PCBP1 enhanced the activity of not only poliovirus internal ribosome-entry site (IRES)-dependent translation but also X-linked inhibitor of apoptosis (XIAP) and KSHV vFLIP IRES. Actually, when ORF57 expression was induced by the expression of replication and transcription activator (RTA) in KSHV-infected cells, the expression of XIAP was enhanced. These results suggest that ORF57 binds to PCBP1 as a functional partner for posttranscriptional regulation and is involved in the regulation of the expression of both cellular and viral genes through IRESs.