EB病毒BGLF4蛋白質激酶急DNAJB6對於病毒DNA引子酶/解旋酶複合體進核調控之探討

徐唯逸

doi:10.6342/NTU201702169

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EB病毒BGLF4蛋白质激酶急DNAJB6对於病毒DNA引子酶/解旋酶复合体进核调控之探讨

Epstein-Barr Virus BGLF4 kinase and DNAJB6 mediated regulation of nuclear targeting of viral DNA primase-helicase complex

徐唯逸 , 硕士　　导师：陈美如　　

英文 DOI： 10.6342/NTU201702169

EB病毒；进核； EBV ； DNAJB6 ； nuclear targeting

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摘要 │ 参考文献 (91) │ 国际计量

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Epstein-Barr virus, which is a world-spread virus, infects over 90% of mankind and is highly associated with several malignancies. As the only protein kinase encoded by EBV, BGLF4, phosphorylates several viral and cellular proteins to optimize the cellular environment for viral replication and nuclear egress of viral nucleocapsid. Previous findings demonstrated that EBV protein kinase, BGLF4, which expressed in EBV early lytic replication, can help the translocation of viral primase-helicase complex from the cytoplasm into nucleus, but the detailed mechanisms remained unknown. Recent studies revealed that a cellular heat shock protein 40 family member (Hsp40s), DNAJB6, is involved in diverse cellular functions including proteins transport and also implicated in numerous pathologies and infectious virus diseases. In this study, we showed that cytoplasmic EBV BSLF1 (primase) could translocate into the nucleus in the presence of DNAJB6a while BBLF2/3 (primase-associated factor) and BBLF4 (helicase) retained in cytoplasm by immuno-fluorescence assay. BSLF1 and BGLF4 was co-immunoprecipitated by DNAJB6a and DNAJB6b, suggesting that DNAJB6a may promote the translocation of EBV primase through direct interaction. Notably, we found that DNAJB6a and DNAJB6b showed different effects on EBV replication. When DNAJB6a was knockdown in EBV positive NA and Akata B cells, it decreased viral DNA replication and virion secretion; while knocking-down DNAJB6b, it increased both viral replication rate and secretion in Akata B cells. The results may emphasize the ratio of DNAJB6 isoforms in affecting viral replication. Moreover, we found that BGLF4 changed the distribution of DNAJB6b from cytoplasm to nucleus. Taken together, we suggested that DNAJB6 and the kinase activity of BGLF4 are required for the nuclear import of BSLF1 and DNAJB6 isoforms affect the viral DNA replication and virion secretion in NA and B cells.

参考文献 ( 91 ) 〈TOP〉

Alvisi, G., D.A. Jans, D. Camozzi, S. Avanzi, A. Loregian, A. Ripalti, and G. Palù. 2013. Regulated transport into the nucleus of herpesviridae DNA replication core proteins. Viruses. 5:2210-2234.
连结：
Amon, W., and P.J. Farrell. 2005. Reactivation of Epstein‐Barr virus from latency. Reviews in medical virology. 15:149-156.
连结：
Andrews, J.F., L.J. Sykora, T.B. Letostak, M.E. Menezes, A. Mitra, S. Barik, L.A. Shevde, and R.S. Samant. 2012. Cellular stress stimulates nuclear localization signal (NLS) independent nuclear transport of MRJ. Experimental cell research. 318:1086-1093.
连结：
Asai, R., A. Kato, K. Kato, M. Kanamori-Koyama, K. Sugimoto, T. Sairenji, Y. Nishiyama, and Y. Kawaguchi. 2006. Epstein-Barr virus protein kinase BGLF4 is a virion tegument protein that dissociates from virions in a phosphorylation-dependent process and phosphorylates the viral immediate-early protein BZLF1. Journal of virology. 80:5125-5134.
连结：
Bukau, B., and A.L. Horwich. 1998. The Hsp70 and Hsp60 chaperone machines. Cell. 92:351-366.
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引用含有DOI的文献

DOI可强化引用精确性、增强学术圈连结，并给予使用者跨平台的良好使用经验，目前在全世界已有超过五千万个对象申请DOI。 如想对DOI的使用与概念有进一步了解，请参考 （ ） 。

DOI可强化引用精确性、增强学术圈连结，并给予使用者跨平台的良好使用经验，目前在全世界已有超过五千万个对象申请DOI。如想对DOI的使用与概念有进一步了解，请参考（）。