Cleavage and secretion of Epstein-Barr virus glycoprotein 42 promote membrane fusion with B lymphocytes.
Cleavage and secretion of Epstein-Barr virus glycoprotein 42 promote membrane fusion with B lymphocytes.
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Epstein-Barr 病毒糖蛋白 42 的裂解和分泌促进与 B 淋巴细胞的膜融合。
DOI：
10.1128/jvi.00195-09
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发表时间：
2009
影响因子：
5.4
通讯作者：
Longnecker,Richard
中科院分区：
文献类型：
--
作者：
Sorem,Jessica;Jardetzky,TheodoreS;Longnecker,Richard
EB病毒（EBV）膜糖蛋白42（gp 42）是病毒通过与B细胞表面上的人类白细胞抗原（HLA）II类结合而进入B淋巴细胞所必需的。EBV gp 42在感染过程中发挥多种作用，包括作为病毒进入B细胞的辅助受体，在膜融合过程中与EBV糖蛋白H（gH）和gL结合，以及通过空间位阻阻断HLA II类肽复合物的T细胞识别。EBV gp 42在感染细胞中以两种形式存在，全长膜结合形式和通过蛋白水解切割产生的可溶形式，所述蛋白水解切割由于N-末端跨膜结构域的缺失而从感染细胞分泌。全长和分泌的gp 42形式都与gH/gL和HLA II类结合，并且gp 42切割的功能意义目前尚不清楚。我们发现，在无病毒的细胞-细胞融合试验中，增强gp 42的分泌促进了与B淋巴细胞的融合，并且gp 42切割位点的突变抑制了膜融合活性。发现gp 42切割的位点与结合gH/gL所必需的gp 42残基在物理上不同。这些结果表明，gp 42的切割和分泌是与B淋巴细胞的膜融合过程所必需的，提供了全长和切割、分泌的gp 42之间的第一个指示的功能差异。
Epstein-Barr virus (EBV) membrane glycoprotein 42 (gp42) is required for viral entry into B lymphocytes through binding to human leukocyte antigen (HLA) class II on the B-cell surface. EBV gp42 plays multiple roles during infection, including acting as a coreceptor for viral entry into B cells, binding to EBV glycoprotein H (gH) and gL during the process of membrane fusion, and blocking T-cell recognition of HLA class II-peptide complexes through steric hindrance. EBV gp42 occurs in two forms in infected cells, a full-length membrane-bound form and a soluble form generated by proteolytic cleavage that is secreted from infected cells due to loss of the N-terminal transmembrane domain. Both the full-length and the secreted gp42 forms bind to gH/gL and HLA class II, and the functional significance of gp42 cleavage is currently unclear. We found that in a virus-free cell-cell fusion assay, enhanced secretion of gp42 promoted fusion with B lymphocytes, and mutation of the site of gp42 cleavage inhibited membrane fusion activity. The site of gp42 cleavage was found to be physically distinct from the residues of gp42 necessary for binding to gH/gL. These results suggest that cleavage and secretion of gp42 are necessary for the process of membrane fusion with B lymphocytes, providing the first indicated functional difference between full-length and cleaved, secreted gp42.