California serogroup Gc (G1) glycoprotein is the principal determinant of pH-dependent cell fusion and entry.
California serogroup Gc (G1) glycoprotein is the principal determinant of pH-dependent cell fusion and entry.
复制标题
加州血清群 Gc (G1) 糖蛋白是 pH 依赖性细胞融合和进入的主要决定因素。
DOI：
10.1016/j.virol.2005.04.026
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Gonzalez-Scarano,Francisco
中科院分区：
文献类型：
--
作者：
Plassmeyer,MatthewL;Soldan,SamanthaS;Stachelek,KarenM;Martin-Garcia,Julio;Gonzalez-Scarano,Francisco
加州正布尼亚病毒血清群的成员，特别是拉克罗斯（LAC）和塔海纳（TAH）病毒，在其蚊媒流行的地区是重要的人类病原体。使用野生型LAC和具有低神经侵袭性的高度神经毒性菌株TAH 181/57的先前研究（Janssen，R.，Gonzalez-Scarano，F.，Nathanson，N.，1984.布尼亚病毒的毒力机制。拉克罗斯强毒株和塔海纳病毒无毒毒株的比较致病性。实验室Invest. 50（4），447-455）已经证明神经侵袭表型映射到M区段，该区段编码两种病毒糖蛋白Gn（G2）和Gc（G1）以及非结构蛋白NSm。为了进一步确定Gn和Gc在融合和进入中的作用，我们使用LAC、TAH 181/57和V22 F（具有缺陷融合功能的LAC的单克隆抗性变体）制备了一组重组M片段构建体。然后在两种替代试验中检测这些M片段构建体的病毒进入：基于T7-荧光素酶表达的细胞-细胞融合试验和基于MLV骨架上布尼亚病毒糖蛋白掺入的假型转导试验。这两种试验均证明Gc是病毒融合和细胞进入的主要决定因素，此外，由氨基酸860-1442描绘的区域（对应于Gc的近膜三分之二）是这些过程的关键。这些结果，再加上结构建模表明Gc和辛德毕斯病毒E1的羧基区域之间的同源性，表明LAC Gc作为II型融合蛋白的功能。
Members of the California serogroup of orthobunyaviruses, particularly La Crosse (LAC) and Tahyna (TAH) viruses, are significant human pathogens in areas where their mosquito vectors are endemic. Previous studies using wild-type LAC and TAH181/57, a highly neurovirulent strain with low neuroinvasiveness (Janssen, R., Gonzalez-Scarano, F., Nathanson, N., 1984. Mechanisms of bunyavirus virulence. Comparative pathogenesis of a virulent strain of La Crosse and an avirulent strain of Tahyna virus. Lab. Invest. 50 (4), 447–455), have demonstrated that the neuroinvasive phenotype maps to the M segment, the segment that encodes the two viral glycoproteins Gn (G2) and Gc (G1), as well as a non-structural protein NSm. To further define the role of Gn and Gc in fusion and entry, we prepared a panel of recombinant M segment constructs using LAC, TAH181/57, and V22F, a monoclonal-resistant variant of LAC with deficient fusion function. These M segment constructs were then tested in two surrogate assays for virus entry: a cell-to-cell fusion assay based on T7-luciferase expression, and a pseudotype transduction assay based on the incorporation of the bunyavirus glycoproteins on an MLV backbone. Both assays demonstrated that Gc is the principal determinant of virus fusion and cell entry, and furthermore that the region delineated by amino acids 860–1442, corresponding to the membrane proximal two-thirds of Gc, is key to these processes. These results, coupled with structural modeling suggesting homologies between the carboxy region of Gc and Sindbis virus E1, suggest that the LAC Gc functions as a type II fusion protein.