Kaposi's sarcoma-associated herpesvirus ORF34 is essential for late gene expression and virus production.
Kaposi's sarcoma-associated herpesvirus ORF34 is essential for late gene expression and virus production.
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DOI：
10.1038/s41598-017-00401-7
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发表时间：
2017-03-23
影响因子：
4.6
通讯作者：
Fujimuro M
中科院分区：
文献类型：
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作者：
Nishimura M;Watanabe T;Yagi S;Yamanaka T;Fujimuro M
卡波西肉瘤相关疱疹病毒（KSHV）是卡波西肉瘤、原发性渗出性淋巴瘤和多中心Castleman病的病原体。KSHV在其宿主中建立终身感染，并在潜伏和裂解感染状态之间交替。在裂解感染期间，裂解相关基因以时间方式表达，并被分类为立即早期、早期和晚期基因转录物。ORF 34是一个早-晚基因，与几种病毒转录相关因子相互作用，但其生理学意义仍然知之甚少。在这里，我们研究了ORF 34在KSHV感染过程中的作用，通过产生ORF 34缺陷的KSHV，使用细菌人工染色体系统。我们的研究结果表明，ORF 34缺陷型KSHV表现出显着减弱晚期基因表达和病毒的生产，但不影响病毒DNA复制。ORF 34与转录因子ORF 18、ORF 24、ORF 31和ORF 66相互作用，以及一种新的ORF 34相互作用伴侣ORF 23。ORF 34的C-末端区域对于与ORF 24的相互作用和病毒产生是重要的。我们的数据支持一个模型，其中ORF 34作为一个枢纽，用于招募病毒转录复合物到ORF 24，以促进晚期病毒基因表达。
Kaposi’s sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease. KSHV establishes a life-long infection in its host and alternates between a latent and lytic infection state. During lytic infection, lytic-related genes are expressed in a temporal manner and categorized as immediate early, early, and late gene transcripts. ORF34 is an early-late gene that interacts with several viral transcription-associated factors, however its physiological importance remains poorly understood. Here, we investigated the role of ORF34 during KSHV infection by generating ORF34-deficient KSHV, using a bacterial artificial chromosome system. Our results reveal that ORF34-deficient KSHV exhibited significantly attenuated late gene expression and viral production but did not affect viral DNA replication. ORF34 interacted with transcription factors ORF18, ORF24, ORF31, and ORF66, and a novel ORF34-interaction partner, ORF23. The C-terminal region of ORF34 was important for interaction with ORF24 and viral production. Our data support a model, in which ORF34 serves as a hub for recruiting a viral transcription complex to ORF24 to promote late viral gene expression.