Activation and degradation of open reading frame 45 by the replication and transcription activator of Kaposi's sarcoma-associated herpesvirus.
Activation and degradation of open reading frame 45 by the replication and transcription activator of Kaposi's sarcoma-associated herpesvirus.
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DOI：
10.1099/vir.0.000125
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发表时间：
2015-07
期刊：
影响因子：
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通讯作者：
Ying Wang;Kai Yu;X. Pei;Tianzheng Zhang;Yuying Guo;C. Wood;Jinzhong Wang
中科院分区：
文献类型：
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作者：
Ying Wang;Kai Yu;X. Pei;Tianzheng Zhang;Yuying Guo;C. Wood;Jinzhong Wang
卡波西肉瘤相关疱疹病毒(KSHV)的开放阅读框45(ORF45)是一种即刻早期磷酸化的被膜蛋白，对病毒逃避宿主免疫监视至关重要。它的表达受病毒复制和转录激活因子(RTA)的上调，RTA是控制从潜伏复制到裂解复制的关键蛋白。我们在这里报道，ORF45的表达不仅被RTA上调，而且还可以被RTA以蛋白酶体依赖的方式降解。RTA通过激活ORF45启动子激活了ORF45，其启动子区域位于第69 271至69 026之间。在慢性感染KSHV的Tre-BCBL-1 RTA细胞中，内源性ORF45蛋白在诱导RTA表达后显著增加，但在诱导后8h迅速下降。我们的研究表明，RTA可能通过微调ORF45和其他病毒/宿主蛋白的水平来控制病毒复制的动力学。
The open reading frame 45 (ORF45) of the Kaposi's sarcoma-associated herpesvirus (KSHV) is an immediate-early phosphorylated tegument protein critical for viral escape from host immune surveillance. Its expression is upregulated by the viral replication and transcription activator (RTA), a key protein that controls the switch from latency to lytic replication. We report here that ORF45 expression was not only upregulated by RTA, but ORF45 could also be degraded by RTA in a proteasome-dependent manner. The ORF45 was activated by RTA via activation of the ORF45 promoter, and the promoter region from nt 69 271 to nt 69 026 was involved. In chronic KSHV infected TRE-BCBL-1 RTA cells, the endogenous ORF45 protein increased dramatically after the induction of RTA expression, but then decreased rapidly after 8 h post-induction. Our study suggests that RTA might control the kinetics of viral replication through fine-tuning of the level of ORF45 and other viral/host proteins.