Herpes Simplex Virus Requires Poly(ADP-Ribose) Polymerase Activity for Efficient Replication and Induces Extracellular Signal-Related Kinase-Dependent Phosphorylation and ICP0-Dependent Nuclear Localization of Tankyrase 1
Herpes Simplex Virus Requires Poly(ADP-Ribose) Polymerase Activity for Efficient Replication and Induces Extracellular Signal-Related Kinase-Dependent Phosphorylation and ICP0-Dependent Nuclear Localization of Tankyrase 1
复制标题
DOI：
10.1128/jvi.05897-11
复制
发表时间：
2012-01-01
影响因子：
5.4
通讯作者：
Nishiyama, Yukihiro
中科院分区：
文献类型：
--
作者：
Li, Zhuan;Yamauchi, Yohei;Nishiyama, Yukihiro
端锚聚合酶 1 是一种聚 (ADP-核糖) 聚合酶 (PARP)，定位于多个亚细胞位点，包括端粒和有丝分裂中心体。有丝分裂过程中端锚聚合酶 1 对核有丝分裂器 (NuMA) 蛋白的聚 (ADP-核糖基) 化对于姐妹端粒解析和有丝分裂纺锤体极的形成至关重要。在间期细胞中，端锚聚合酶 1 存在于细胞质中，但其在其中的作用尚不清楚。在这项研究中，我们发现单纯疱疹病毒 (HSV) 感染诱导端聚合酶 1 的广泛修饰，但不诱导端聚合酶 2。这种修饰依赖于 HSV 感染触发的细胞外信号调节激酶 (ERK) 活性。 HSV-1 感染后，端锚聚合酶 1 被募集至细胞核。在感染的早期阶段，端锚聚合酶 1 与 ICP0 共定位，随后定位在 HSV 复制区室中，该复制区室在感染 HSV-1 ICP0 缺失突变体 R7910 的细胞中被阻断。在没有感染的情况下，ICP0 与端聚合酶 1 相互作用并有效促进其核定位。 HSV 在耗尽端锚聚合酶 1 和 2 的细胞中无法有效复制。此外，端锚聚合酶 PARP 活性抑制剂 XAV939 将病毒滴度降低至对照值的 2% 至 5%。我们得出结论，HSV 以 ICP0 和 ERK 依赖性方式靶向坦聚合酶 1，以促进其复制。
Tankyrase 1 is a poly(ADP-ribose) polymerase (PARP) which localizes to multiple subcellular sites, including telomeres and mitotic centrosomes. Poly(ADP-ribosyl) ation of the nuclear mitotic apparatus (NuMA) protein by tankyrase 1 during mitosis is essential for sister telomere resolution and mitotic spindle pole formation. In interphase cells, tankyrase 1 resides in the cytoplasm, and its role therein is not well understood. In this study, we found that herpes simplex virus (HSV) infection induced extensive modification of tankyrase 1 but not tankyrase 2. This modification was dependent on extracellular signal-regulated kinase (ERK) activity triggered by HSV infection. Following HSV-1 infection, tankyrase 1 was recruited to the nucleus. In the early phase of infection, tankyrase 1 colocalized with ICP0 and thereafter localized within the HSV replication compartment, which was blocked in cells infected with the HSV-1 ICP0-null mutant R7910. In the absence of infection, ICP0 interacted with tankyrase 1 and efficiently promoted its nuclear localization. HSV did not replicate efficiently in cells depleted of both tankyrases 1 and 2. Moreover, XAV939, an inhibitor of tankyrase PARP activity, decreased viral titers to 2 to 5% of control values. We concluded that HSV targets tankyrase 1 in an ICP0-and ERK-dependent manner to facilitate its replication.