Activation of PI3K/AKT and ERK MAPK signal pathways is required for the induction of lytic cycle replication of Kaposi's sarcoma-associated herpesvirus by herpes simplex virus type 1.
Activation of PI3K/AKT and ERK MAPK signal pathways is required for the induction of lytic cycle replication of Kaposi's sarcoma-associated herpesvirus by herpes simplex virus type 1.
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1 型单纯疱疹病毒诱导卡波西肉瘤相关疱疹病毒裂解周期复制需要激活 PI3K/AKT 和 ERK MAPK 信号通路
DOI：
10.1186/1471-2180-11-240
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发表时间：
2011-10-27
期刊：
影响因子：
4.2
通讯作者：
Lu C
中科院分区：
文献类型：
--
作者：
Qin D;Feng N;Fan W;Ma X;Yan Q;Lv Z;Zeng Y;Zhu J;Lu C
Kaposi肉瘤相关疱疹病毒(KSHV)与多种获得性免疫缺陷综合征相关的恶性肿瘤有关，包括Kaposi肉瘤(KS)、原发渗出性淋巴瘤(PEL)和一组多中心性Castleman病。病毒裂解复制的调控对KS的发生和发展至关重要。最近，我们报道了单纯疱疹病毒1型(HSV-1)是激活KSHV裂解周期复制的重要辅因子。结果通过转染一系列显性负性突变体和蛋白表达载体，并使用药物抑制剂，我们发现Janus kinas1(JAK1)/信号转导和转录激活因子3(STAT3)或JAK1/STAT6信号通路都不能调控HSV-1诱导的KSHV复制。然而，单纯疱疹病毒1型感染BCBL-1细胞后，激活了磷脂酰肌醇3-激酶/蛋白激酶B途径，失活的第10号染色体缺失的磷酸酶和张力蛋白同源物(PTEN)和糖原合成酶β(GSK-3β)。PTEN/PI3K/AKT/GSK-3β通路参与了HSV1诱导的KSHV再激活过程。结论HSV-1感染激活了PI3K/AKT和ERK MAPK信号通路，进而促进了KSHV的再激活，进一步揭示了控制KSHV裂解复制的分子机制，特别是在HSV-1和KSHV混合感染的情况下。
BackgroundKaposi's sarcoma-associated herpesvirus (KSHV) is causally linked to several acquired immunodeficiency syndrome-related malignancies, including Kaposi's sarcoma (KS), primary effusion lymphoma (PEL) and a subset of multicentric Castleman's disease. Regulation of viral lytic replication is critical to the initiation and progression of KS. Recently, we reported that herpes simplex virus type 1 (HSV-1) was an important cofactor that activated lytic cycle replication of KSHV. Here, we further investigated the possible signal pathways involved in HSV-1-induced reactivation of KSHV.ResultsBy transfecting a series of dominant negative mutants and protein expressing constructs and using pharmacologic inhibitors, we found that either Janus kinase 1 (JAK1)/signal transducer and activator of transcription 3 (STAT3) or JAK1/STAT6 signaling failed to regulate HSV-1-induced KSHV replication. However, HSV-1 infection of BCBL-1 cells activated phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB, also called AKT) pathway and inactivated phosphatase and tensin homologue deleted on chromosome ten (PTEN) and glycogen synthase kinase-3β (GSK-3β). PTEN/PI3K/AKT/GSK-3β pathway was found to be involved in HSV-1-induced KSHV reactivation. Additionally, extracellular signal-regulated protein kinase (ERK) mitogen-activated protein kinase (MAPK) pathway also partially contributed to HSV-1-induced KSHV replication.ConclusionsHSV-1 infection stimulated PI3K/AKT and ERK MAPK signaling pathways that in turn contributed to KSHV reactivation, which provided further insights into the molecular mechanism controlling KSHV lytic replication, particularly in the context of HSV-1 and KSHV co-infection.
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影响因子：
4.3
作者：
Montaner, Silvia
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