Differences in the Regulatory and Functional Effects of the Us3 Protein Kinase Activities of Herpes Simplex Virus 1 and 2
Differences in the Regulatory and Functional Effects of the Us3 Protein Kinase Activities of Herpes Simplex Virus 1 and 2
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DOI：
10.1128/jvi.00993-09
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发表时间：
2009-11-15
影响因子：
5.4
通讯作者：
Kawaguchi, Yasushi
中科院分区：
文献类型：
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作者：
Morimoto, Tomomi;Arii, Jun;Kawaguchi, Yasushi
由单纯疱疹病毒 1 (HSV-1) 和 2 (HSV-2) 编码的 Us3 蛋白激酶是丝氨酸/苏氨酸蛋白激酶，在体内病毒复制和致病性中发挥关键作用。在本研究中，我们研究了 HSV-1 和 HSV-2 Us3 蛋白激酶生物学特性的差异，并证明 HSV-2 Us3 不具有某些 HSV-1 Us3 激酶功能，包括控制核衣壳的核出口、UL31 和 UL34 的定位以及病毒包膜糖蛋白 B 的细胞表面表达。与 HSV-2 Us3 对这些功能不太重要的观察结果一致，HSV-2 Us3 的作用脑内接种后小鼠毒力激酶活性远低于HSV-1 Us3。此外，我们发现，HSV-2 Us3 中与 HSV-1 Us3 中可自磷酸化的位点相对应的位点（第 147 位天冬氨酸）的丙氨酸取代消除了 HSV-2 Us3 激酶活性。因此，Us3 激酶活性的调节和功能作用在 HSV-1 和 HSV-2 之间是不同的。
Us3 protein kinases encoded by herpes simplex virus 1 (HSV-1) and 2 (HSV-2) are serine/threonine protein kinases and play critical roles in viral replication and pathogenicity in vivo. In the present study, we investigated differences in the biological properties of HSV-1 and HSV-2 Us3 protein kinases and demonstrated that HSV-2 Us3 did not have some of the HSV-1 Us3 kinase functions, including control of nuclear egress of nucleocapsids, localization of UL31 and UL34, and cell surface expression of viral envelope glycoprotein B. In agreement with the observations that HSV-2 Us3 was less important for these functions, the effect of HSV-2 Us3 kinase activity on virulence in mice following intracerebral inoculation was much lower than that of HSV-1 Us3. Furthermore, we showed that alanine substitution in HSV-2 Us3 at a site (aspartic acid at position 147) corresponding to one that can be autophosphorylated in HSV-1 Us3 abolished HSV-2 Us3 kinase activity. Thus, the regulatory and functional effects of Us3 kinase activity are different between HSV-1 and HSV-2.