Epstein-Barr virus latent membrane protein-1 (LMP-1) and lytic LMP-1 localization in plasma membrane-derived extracellular vesicles and intracellular virions.
Epstein-Barr virus latent membrane protein-1 (LMP-1) and lytic LMP-1 localization in plasma membrane-derived extracellular vesicles and intracellular virions.
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DOI：
10.1099/vir.0.19156-0
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发表时间：
2003-08
期刊：
影响因子：
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通讯作者：
Golnar Vazirabadi;Timothy R. Geiger;W. Coffin;Jennifer M. Martin
中科院分区：
文献类型：
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作者：
Golnar Vazirabadi;Timothy R. Geiger;W. Coffin;Jennifer M. Martin
eb病毒（EBV）是一种与许多恶性肿瘤相关的人类疱疹病毒。EBV在体外建立了人B细胞的潜伏感染，感染的淋巴母细胞样细胞由于病毒激活细胞信号通路而无限增殖。潜伏感染的细胞表达一种叫做潜伏膜蛋白-1 （LMP-1）的病毒癌蛋白。LMP-1向感染的B细胞发出增殖和存活信号。从延迟到裂解复制的转换与n端截断的LMP-1的上调有关，称为裂解性LMP-1 （lyLMP-1）。为了更好地了解LMP-1蛋白功能与病毒生命周期的关系，我们在感染的B细胞中精确定位了LMP-1和lyLMP-1。潜伏感染细胞的免疫电镜显示LMP-1定位于质膜上的离散斑块。出乎意料的是，免疫金标记的LMP-1出现在从质膜出芽到细胞外空间的囊泡中，以及在条件培养基中从感染细胞积累的小膜囊泡中。LyLMP-1免疫标记仅在含有可检测到的细胞内病毒颗粒的B95-8细胞中观察到，并且在裂解周期诱导后，在核膜早期和质膜晚期大量存在。LyLMP-1在病毒出芽部位也观察到免疫反应性，并与细胞内病毒粒子相关，提示LyLMP-1通过核膜出芽时可能被纳入细胞质病毒粒子。
Epstein-Barr virus (EBV) is a human herpesvirus associated with a number of malignancies. EBV establishes a latent infection in human B cells in vitro, and infected lymphoblastoid cells proliferate indefinitely as a result of virus activation of cellular signalling pathways. Latently infected cells express a viral oncoprotein called the latent membrane protein-1 (LMP-1). LMP-1 signals both proliferative and survival signals to the infected B cell. The switch from latency to lytic replication is associated with upregulation of an N-terminally truncated LMP-1, called lytic LMP-1 (lyLMP-1). To understand better the relationship between LMP-1 protein function and the virus life cycle, LMP-1 and lyLMP-1 were precisely localized in infected B cells. Immunoelectron microscopy of latently infected cells revealed LMP-1 localized in discrete patches in the plasma membrane. Unexpectedly, immunogold-labelled LMP-1 was found in vesicles budding from the plasma membrane into the extracellular space and in small membrane vesicles accumulating in conditioned medium from infected cells. LyLMP-1 immunolabelling was observed only in B95-8 cells harbouring detectable intracellular virus particles and was abundant in the nuclear membrane early, and in the plasma membrane late, following lytic cycle induction. LyLMP-1 immunoreactivity was also observed at sites of virus budding and associated with intracellular virions, suggesting that lyLMP-1 might be incorporated into cytoplasmic virions when budding through the nuclear membrane.