Gershburg Edward, Raffa Salvatore, Torrisi Maria Rosaria, Pagano Joseph S
Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, CB #7295, Chapel Hill, NC 27599-7295, USA.
J Virol. 2007 May;81(10):5407-12. doi: 10.1128/JVI.02398-06. Epub 2007 Mar 14.
The Epstein-Barr virus (EBV) BGLF4 gene product is a protein kinase (PK). Although this kinase has been characterized and several of its targets have been identified, its biological role remains enigmatic. We have generated and assessed a BGLF4 knockdown phenotype by means of RNA interference and report the following: (i) BGLF4-targeting small interfering RNA effectively inhibited the expression of its product, the viral PK, during lytic reactivation, (ii) BGLF4 knockdown partially inhibited viral DNA replication and expression of selected late viral genes, (iii) the absence of EBV PK resulted in retention of the viral nucleocapsids in the nuclei, and (iv) as a result of the nuclear retention, release of infectious virions is significantly retarded. Our results provide evidence that EBV PK plays an important role in nuclear egress of the virus and ultimately is crucial for lytic virus replication.
爱泼斯坦-巴尔病毒(EBV)的BGLF4基因产物是一种蛋白激酶(PK)。尽管这种激酶已被表征且其一些靶点已被确定,但其生物学作用仍然成谜。我们通过RNA干扰产生并评估了BGLF4敲低表型,结果如下:(i)靶向BGLF4的小干扰RNA在裂解性再激活期间有效抑制了其产物(病毒PK)的表达;(ii)BGLF4敲低部分抑制了病毒DNA复制和所选晚期病毒基因的表达;(iii)EBV PK的缺失导致病毒核衣壳滞留在细胞核中;(iv)由于核滞留,感染性病毒粒子的释放显著延迟。我们的结果表明,EBV PK在病毒的核输出中起重要作用,最终对裂解性病毒复制至关重要。