Narita Yohei, Sugimoto Atsuko, Kawashima Daisuke, Watanabe Takahiro, Kanda Teru, Kimura Hiroshi, Tsurumi Tatsuya, Murata Takayuki
1] Division of Virology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan [2] Department of Virology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Division of Virology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan.
Sci Rep. 2015 Jun 30;5:11767. doi: 10.1038/srep11767.
Epstein-Barr virus (EBV) is associated with several malignancies, including Burkitt lymphoma and nasopharyngeal carcinoma. To overcome such disorders, understanding the molecular mechanisms of the EBV replication is important. The EBV DNA polymerase (Pol) is one of the essential factors for viral lytic DNA replication. Although it is well known that its C-terminal half, possessing DNA polymerase and 3'-5' exonuclease activity, is highly conserved among Family B Pols, the NH2-terminal half has yet to be characterized in detail. In this study, we show that a stretch of hydrophobic amino acids within the pre-NH2-terminal domain of EBV Pol plays important role. In addition, we could identify the most essential residue for replication in the motif. These findings will shed light on molecular mechanisms of viral DNA synthesis and will help to develop new herpesviruses treatments.
爱泼斯坦-巴尔病毒(EBV)与多种恶性肿瘤有关,包括伯基特淋巴瘤和鼻咽癌。为了克服这些疾病,了解EBV复制的分子机制很重要。EBV DNA聚合酶(Pol)是病毒裂解性DNA复制的关键因素之一。虽然已知其具有DNA聚合酶和3'-5'核酸外切酶活性的C端一半在B族聚合酶中高度保守,但NH2端一半尚未得到详细表征。在本研究中,我们表明EBV Pol的前NH2端结构域内的一段疏水氨基酸发挥着重要作用。此外,我们能够在该基序中确定复制最关键的残基。这些发现将阐明病毒DNA合成的分子机制,并有助于开发新的疱疹病毒治疗方法。