SV40 Polyomavirus Activates the Ras-MAPK Signaling Pathway for Vacuolization, Cell Death, and Virus Release.
SV40 Polyomavirus Activates the Ras-MAPK Signaling Pathway for Vacuolization, Cell Death, and Virus Release.
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DOI：
10.3390/v12101128
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发表时间：
2020-10-05
期刊：
影响因子：
--
通讯作者：
DiMaio D
中科院分区：
文献类型：
--
作者：
Motamedi N;Sewald X;Luo Y;Mothes W;DiMaio D
多瘤病毒是一个小型无包膜DNA病毒家族，可在免疫抑制个体中引起严重疾病。用SV 40（一种研究充分的模型多瘤病毒）进行的研究已经揭示了宿主蛋白在多瘤病毒进入和运输到细胞核中、在病毒转录和DNA复制中以及在细胞转化中的作用。与此相反，很少有人知道宿主因子或细胞信号通路参与生产性感染的后期步骤，导致后代多瘤病毒的释放。我们以前表明，细胞质空泡化，一个特征性的晚期细胞病变效应的SV 40感染，依赖于主要的病毒衣壳蛋白VP 1和其细胞表面神经节苷脂受体GM 1之间的特异性相互作用。在这里，我们发现，在感染后期，SV 40激活了一个信号级联反应，在允许的猴CV-1细胞涉及Ras，Rac 1，MKK 4和JNK刺激SV 40特异性细胞质空泡化和随后的细胞裂解和病毒释放。抑制该信号通路的各个组分可抑制空泡化、裂解和病毒释放，即使发生高水平的细胞内病毒复制。对SV 40诱导的空泡化和病毒释放的这一途径的鉴定为无包膜病毒感染的后期步骤提供了新的见解。
Polyomaviruses are a family of small, non-enveloped DNA viruses that can cause severe disease in immunosuppressed individuals. Studies with SV40, a well-studied model polyomavirus, have revealed the role of host proteins in polyomavirus entry and trafficking to the nucleus, in viral transcription and DNA replication, and in cell transformation. In contrast, little is known about host factors or cellular signaling pathways involved in the late steps of productive infection leading to release of progeny polyomaviruses. We previously showed that cytoplasmic vacuolization, a characteristic late cytopathic effect of SV40 infection, depends on the specific interaction between the major viral capsid protein VP1 and its cell surface ganglioside receptor GM1. Here, we show that, late during infection, SV40 activates a signaling cascade in permissive monkey CV-1 cells involving Ras, Rac1, MKK4, and JNK to stimulate SV40-specific cytoplasmic vacuolization and subsequent cell lysis and virus release. Inhibition of individual components of this signaling pathway inhibits vacuolization, lysis, and virus release, even though high-level intracellular virus replication occurs. Identification of this pathway for SV40-induced vacuolization and virus release provides new insights into the late steps of non-enveloped virus infection.
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影响因子：
6.4
作者：
Luo Y;Motamedi N;Magaldi TG;Gee GV;Atwood WJ;DiMaio D
通讯作者：
DiMaio D
影响因子：
5.4
作者：
CLAYSON, ET;BRANDO, LVJ;COMPANS, RW
通讯作者：
COMPANS, RW
影响因子：
5.4
作者：
Magaldi, Thomas G.;Buch, Michael H. C.;DiMaio, Daniel
通讯作者：
DiMaio, Daniel
DOI：
10.3390/v8090242
发表时间：
2016-08-29
期刊：
Viruses
影响因子：
--
作者：
Dupzyk A;Tsai B
通讯作者：
Tsai B
影响因子：
64.8
作者：
Pelkmans, L;Fava, E;Zerial, M
通讯作者：
Zerial, M