Associating bovine herpesvirus 1 envelope glycoprotein gD with activated phospho-PLC-γ1(S1248).
Associating bovine herpesvirus 1 envelope glycoprotein gD with activated phospho-PLC-γ1(S1248).
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DOI：
10.1128/spectrum.01963-23
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发表时间：
2023-09-01
影响因子：
3.7
通讯作者：
Zhu, Liqian
中科院分区：
文献类型：
--
作者：
Liu, Chang;Yuan, Weifeng;Yang, Hao;Ni, Junqing;Tang, Linke;Zhao, Heci;Neumann, Donna;Ding, Xiuyan;Zhu, Liqian
磷脂酶C γ1 （PLC-γ1）可能位于不同的亚细胞位置，如细胞质、质膜和细胞核，具有不同的生物学功能。牛疱疹病毒1（BoHV-1）产生性感染激活PLC-γ -1信号，证实了磷酸化的PLC-γ -1 Ser1248蛋白水平升高[p-PLC-γ -1 (S1248)]，这有利于病毒产生性感染。在这里，我们首次报道了高尔基体也含有活化的p-PLC-γ1（S1248）。BoHV-1生产感染后期（24 hpi）增加了p-PLC-γ1（S1248）在高尔基体中的积累，在共聚焦显微镜下观察到p-PLC-γ1（S1248）形成突出的斑点。共免疫沉淀研究表明，高尔基p-PLC-γ1（S1248）与病毒蛋白gD特异性相关，而与gC不相关。此外，我们发现p-PLC-γ1（S1248）与质膜相关病毒粒子和释放的病毒粒子一致相关。在病毒感染终点前，用PLC-γ - 1特异性抑制剂U73122处理病毒感染细胞4小时，我们发现病毒蛋白gD被困在高尔基体中，这表明PLC-γ - 1信号可能促进了子代病毒粒子从该细胞器转运。这些发现为PLC-γ -1信号传导与BoHV-1复制之间的相互作用提供了新的见解。牛疱疹病毒1型（BoHV-1）产生性感染增加磷酸化磷脂酶C γ1 Ser1248蛋白水平[p-PLC-γ1(S1248)]。然而，它是否引起p-PLC-γ1(S1248)定位的任何变化尚不清楚。在这里，我们首次发现部分p-PLC-γ1（S1248）驻留在高尔基体中，在那里积聚被病毒感染增强。p-PLC-γ1（S1248）在高尔基体和细胞质膜中都与病毒粒子一致存在，部分通过与gD结合。令人惊讶的是，它还与释放的病毒粒子有关。值得注意的是，这是首次证实BoHV-1病毒粒子结合宿主蛋白。p-PLC-γ1（S1248）似乎在子代病毒粒子从高尔基体向质膜运输并释放到细胞膜外的过程中起着护送作用。此外，我们发现活化的p-PLC-γ1（S1248）可能与病毒粒子从高尔基体转运有关，这可能代表了一种调节病毒生产感染的新机制。
Phospholipase C gamma 1 (PLC-γ1) may locate at distinct subcellular locations, such as cytosol, plasma membrane, and nucleus for varied biological functions. Bovine herpesvirus 1 (BoHV-1) productive infection activates PLC-γ1 signaling, as demonstrated by increased protein levels of phosphorylated-PLC-γ1 at Ser1248 [p-PLC-γ1(S1248)], which benefits virus productive infection. Here, for the first time, we reported that Golgi apparatus also contains activated p-PLC-γ1(S1248). And BoHV-1 productive infection at later stages (24 hpi) increased the accumulation of p-PLC-γ1(S1248) in the Golgi apparatus, where p-PLC-γ1(S1248) forms highlighted puncta observed via a confocal microscope. Coimmunoprecipitation studies demonstrated that the Golgi p-PLC-γ1(S1248) is specifically associated with the viral protein gD but not gC. In addition, we found that p-PLC-γ1(S1248) is consistently associated with both the plasma membrane-associated virions and the released virions. When the virus-infected cells were treated with PLC-γ1-specific inhibitor, U73122, for a short duration of 4 hours prior to the endpoint of virus infection, we found that the viral protein gD was trapped in the Golgi apparatus, suggesting that the PLC-γ1 signaling may facilitate trafficking of progeny virions out of this organelle. These findings provide a novel insight into the interplay between PLC-γ1 signaling and BoHV-1 replication. Bovine herpesvirus 1 (BoHV-1) productive infection increases protein levels of phosphorylated-phospholipase C gamma 1 at Ser1248 [p-PLC-γ1(S1248)]. However, whether it causes any variations to p-PLC-γ1(S1248) localization is not well understood. Here, for the first time, we found that partial p-PLC-γ1(S1248) is residing in the Golgi apparatus, where the accumulation is enhanced by virus infection. p-PLC-γ1(S1248) is consistently associated with virions, partially via binding to gD, in both the Golgi apparatus and cytoplasm membranes. Surprisingly, it also associates with the released virions. Of note, this is the first evidenced BoHV-1 virion-bound host protein. It seems that p-PLC-γ1(S1248) works as an escort during trafficking of progeny virions out of Golgi apparatus to the plasma membranes as well as releasing outside of the cell membranes. Furthermore, we showed that the activated p-PLC-γ1(S1248) is potentially implicated in the transport of virions out of Golgi apparatus, which may represent a novel mechanism to regulate virus productive infection.
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影响因子：
2.9
作者：
BALDASSARE, JJ;HENDERSON, PA;FISHER, GJ
通讯作者：
FISHER, GJ
影响因子：
3.1
作者：
Karger, A;Bettin, B;Mettenleiter, TC
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Mettenleiter, TC
影响因子：
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作者：
Raimondi, Claudio;Chikh, Anissa;Falasca, Marco
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作者：
Kot, Magdalena;Mazurkiewicz, Ewa;Wiktor, Maciej;Wiertelak, Wojciech;Mazur, Antonina Joanna;Rahalevich, Andrei;Olczak, Mariusz;Maszczak-Seneczko, Dorota
通讯作者：
Maszczak-Seneczko, Dorota
影响因子：
--
作者：
Hodgson, P D;Aich, P;Manuja, A;Hokamp, K;Roche, F M;Brinkman, F S L;Potter, A;Babiuk, L A;Griebel, P J
通讯作者：
Griebel, P J