Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Division of Viral Infection, Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Adv Exp Med Biol. 2018;1045:45-62. doi: 10.1007/978-981-10-7230-7_3.
All members of the Alphaherpesvirinae subfamily encode a serine/threonine kinase, designated Us3, which is not conserved in the other subfamilies. Us3 is a significant virulence factor for herpes simplex virus type 1 (HSV-1), which is one of the best-characterized members of the Alphaherpesvirinae family. Accumulating evidence indicates that HSV-1 Us3 is a multifunctional protein that plays various roles in the viral life cycle by phosphorylating a number of viral and cellular substrates. Therefore, the identification of Us3 substrates is directly connected to understanding Us3 functions and mechanisms. To date, more than 23 phosphorylation events upregulated by HSV-1 Us3 have been reported. However, few of these have been shown to be both physiological substrates of Us3 in infected cells and directly linked with Us3 functions in infected cells. In this chapter, we summarize the 12 physiological substrates of Us3 and the Us3-mediated functions. Furthermore, based on the identified phosphorylation sites of Us3 or Us3 homolog physiological substrates, we reverified consensus phosphorylation target sequences on the physiological substrates of Us3 and Us3 homologs in vitro and in infected cells. This information might aid the further identification of novel Us3 substrates and as yet unidentified Us3 functions.
α疱疹病毒亚科的所有成员都编码一种丝氨酸/苏氨酸激酶，称为 Us3，它在其他亚科中并不保守。Us3 是单纯疱疹病毒 1 型（HSV-1）的重要毒力因子，HSV-1 是α疱疹病毒亚科中研究最充分的成员之一。越来越多的证据表明，HSV-1 的 Us3 是一种多功能蛋白，通过磷酸化许多病毒和细胞底物在病毒生命周期中发挥各种作用。因此，Us3 底物的鉴定直接关系到理解 Us3 的功能和机制。迄今为止，已报道了超过 23 种由 HSV-1 Us3 上调的磷酸化事件。然而，其中很少有被证明是感染细胞中 Us3 的生理底物，并且与感染细胞中 Us3 的功能直接相关。在本章中，我们总结了 12 种 Us3 的生理底物及其介导的功能。此外，基于已鉴定的 Us3 或 Us3 同源物生理底物的磷酸化位点，我们在体外和感染细胞中重新验证了 Us3 和 Us3 同源物生理底物上的保守磷酸化靶序列。这些信息可能有助于进一步鉴定新的 Us3 底物和尚未鉴定的 Us3 功能。
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