Kaposi's sarcoma-associated herpesvirus open reading frame 50/Rta protein activates the entire viral lytic cycle in the HH-B2 primary effusion lymphoma cell line

Kaposi's sarcoma-associated herpesvirus open reading frame 50/Rta protein activates the entire viral lytic cycle in the HH-B2 primary effusion lymphoma cell line
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DOI:
10.1128/jvi.74.13.6207-6212.2000
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发表时间:
2000-07-01
影响因子:
5.4
通讯作者:
Miller, G
Miller, G
中科院分区:
医学2区
文献类型:
--
作者:
Gradoville, L;Gerlach, J;Miller, G

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卡波济肉瘤相关疱疹病毒(Kaposi ′ ssarcoma-associated herpesvirus,KSHV)的基因产物Rta主要编码在开放阅读框50(ORF 50)中,能够激活病毒裂解周期基因的表达。在以前的研究中没有证明的是KSHV Rta是否有能力启动整个病毒裂解生命周期,包括裂解病毒DNA复制、具有适当动力学的晚期基因表达和病毒释放。在新近建立原发性渗出性淋巴瘤(PEL)细胞系HH-B2中,KSHV ORF 50表现为立即早期基因,并自身刺激其表达。KSHV Rta诱导的晚期基因ORF 65和K8.1的表达被病毒DNA聚合酶抑制剂膦酰乙酸消除。转染KSHV Rta后,HH-BZ细胞中的耐脱氧核糖核酸酶病毒DNA产量增加。因此,ORF 50表达质粒的引入足以在培养的PEL细胞中驱动裂解循环完成。
Rta, the gene product of Kaposi's sarcoma-associated herpesvirus (KSHV) encoded mainly in open reading frame 50 (ORF50), is capable of activating expression of viral lytic cycle genes. What was not demonstrated in previous studies was whether KSHV Rta was competent to initiate the entire viral lytic life cycle including lytic viral DNA replication, late-gene expression with appropriate kinetics, and virus release. in HH-B2, a newly established primary effusion lymphoma (PEL) cell line, KSHV ORF50 behaved as an immediate-early gene and autostimulated its own expression. Expression of late genes, ORF65, and K8.1 induced by KSHV Rta was eliminated by phosphonoacetic acid, an inhibitor of viral DNA polymerase. Transfection of KSHV Rta increased the production of encapsidated DNase-resistant viral DNA from HH-BZ cells. Thus, introduction of an ORF50 expression plasmid is sufficient to drive the lytic cycle to completion in cultured PEL cells.