Haruki Hirohito, Okuwaki Mitsuru, Miyagishi Makoto, Taira Kazunari, Nagata Kyosuke
Department of Infection Biology, Graduate School of Comprehensive Human Sciences and Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan.
J Virol. 2006 Jan;80(2):794-801. doi: 10.1128/JVI.80.2.794-801.2006.
The adenovirus genome complexed with viral core protein VII (adenovirus DNA-protein VII complex) at least is the bona fide template for transcription of adenovirus early genes. It is believed that the highly basic protein VII, like cellular histones, is a negative regulator for genome functions. Analyses with in vitro replication and transcription systems using the adenovirus DNA-protein VII complex have revealed that remodeling of the complex is crucial for efficient DNA replication and transcription. We identified host acidic proteins, template-activating factor I (TAF-I), TAF-II, and TAF-III as stimulatory factors for replication from the adenovirus DNA-protein VII complex. Recently, it was reported that the adenovirus DNA interacts with TAF-I and pp32, another host acidic protein (Y. Xue, J. S. Johnson, D. A. Ornelles, J. Lieberman, and D. A. Engel, J. Virol. 79:2474-2483, 2005). We found that TAF-I interacts and colocalizes with protein VII in adenovirus-infected cells during the early phases of infection, but pp32 does not. Although pp32 had the potential ability to interact with protein VII, pp32 did not remodel the adenovirus DNA-protein VII complex in vitro. Small interfering RNA-mediated knockdown of TAF-I expression leads to the delay of the transcription timing of early genes. These results provide evidence that TAF-I plays an important role in the early stages of the adenovirus infection cycle.
与病毒核心蛋白VII复合的腺病毒基因组(腺病毒DNA-蛋白VII复合物)至少是腺病毒早期基因转录的真正模板。据信,高度碱性的蛋白VII与细胞组蛋白一样,是基因组功能的负调节因子。使用腺病毒DNA-蛋白VII复合物的体外复制和转录系统分析表明,该复合物的重塑对于有效的DNA复制和转录至关重要。我们鉴定出宿主酸性蛋白模板激活因子I(TAF-I)、TAF-II和TAF-III是腺病毒DNA-蛋白VII复合物复制的刺激因子。最近,有报道称腺病毒DNA与TAF-I和另一种宿主酸性蛋白pp32相互作用(Y. Xue、J. S. Johnson、D. A. Ornelles、J. Lieberman和D. A. Engel,《病毒学杂志》79:2474-2483,2005年)。我们发现,在感染早期,TAF-I在腺病毒感染细胞中与蛋白VII相互作用并共定位,但pp32并非如此。尽管pp32具有与蛋白VII相互作用的潜在能力,但pp32在体外并未重塑腺病毒DNA-蛋白VII复合物。小干扰RNA介导的TAF-I表达敲低导致早期基因转录时间延迟。这些结果证明TAF-I在腺病毒感染周期的早期阶段发挥重要作用。