Shi Xiaohong, Lappin David F, Elliott Richard M
Division of Virology, Institute of Biomedical and Life Sciences, University of Glasgow, Church St., Glasgow G11 5JR, Scotland, United Kingdom.
J Virol. 2004 Oct;78(19):10793-802. doi: 10.1128/JVI.78.19.10793-10802.2004.
The membrane glycoproteins (Gn and Gc) of Bunyamwera virus (BUN; family Bunyaviridae) accumulate in the Golgi complex, where virion maturation occurs. The Golgi targeting and retention signal has previously been shown to reside within the Gn protein. A series of truncated Gn and glycoprotein precursor cDNAs were constructed by progressively deleting the coding region of the transmembrane domain (TMD) and the cytoplasmic tail. We also constructed chimeric proteins of BUN Gc, enhanced green fluorescent protein (EGFP), and human respiratory syncytial virus (HRSV) fusion (F) protein that contain the Gn TMD with various lengths of its adjacent cytoplasmic tails. The subcellular localization of mutated BUN glycoproteins and chimeric proteins was investigated by double-staining immunofluorescence with antibodies against BUN glycoproteins or the HRSV F protein and with antibodies specific for the Golgi complex. The results revealed that Gn and all truncated Gn proteins that contained the intact TMD (residues 206 to 224) were able to translocate to the Golgi complex and also rescued the Gc protein, which is retained in the endoplasmic reticulum when expressed alone, to this organelle. The rescued Gc proteins acquired endo-beta-N-acetylglucosaminidase H resistance. The Gn TMD could also target chimeric EGFP to the Golgi and retain the F protein, which is characteristically expressed on the surface of HRSV-infected cells, in the Golgi. However, chimeric BUN Gc did not translocate to the Golgi, suggesting that an interaction with Gn is involved in Golgi retention of the Gc protein. Collectively, these data demonstrate that the Golgi targeting and retention signal of BUN glycoproteins resides in the TMD of the Gn protein.
布尼亚姆韦拉病毒(BUN;布尼亚病毒科)的膜糖蛋白(Gn和Gc)在高尔基体复合体中积累,病毒粒子在此处成熟。先前已证明高尔基体靶向和保留信号位于Gn蛋白内。通过逐步删除跨膜结构域(TMD)和细胞质尾的编码区域,构建了一系列截短的Gn和糖蛋白前体cDNA。我们还构建了布尼亚姆韦拉病毒Gc、增强型绿色荧光蛋白(EGFP)和人类呼吸道合胞病毒(HRSV)融合(F)蛋白的嵌合蛋白,这些嵌合蛋白包含具有不同长度相邻细胞质尾的Gn TMD。通过用抗布尼亚姆韦拉病毒糖蛋白或HRSV F蛋白的抗体以及针对高尔基体复合体的特异性抗体进行双重染色免疫荧光,研究了突变的布尼亚姆韦拉病毒糖蛋白和嵌合蛋白的亚细胞定位。结果显示,Gn以及所有包含完整TMD(第206至224位氨基酸残基)的截短Gn蛋白都能够转运至高尔基体复合体,并且还能将单独表达时保留在内质网中的Gc蛋白拯救至该细胞器。拯救后的Gc蛋白获得了对β-N-乙酰葡糖胺糖苷酶H的抗性。Gn TMD还可将嵌合的EGFP靶向至高尔基体,并将通常在HRSV感染细胞表面表达的F蛋白保留在高尔基体中。然而,嵌合的布尼亚姆韦拉病毒Gc并未转运至高尔基体,这表明与Gn的相互作用参与了Gc蛋白在高尔基体中的保留。总体而言,这些数据表明布尼亚姆韦拉病毒糖蛋白的高尔基体靶向和保留信号位于Gn蛋白的TMD中。