Differential Effects on Cell Fusion Activity of Mutations in Herpes Simplex Virus 1 Glycoprotein B (gB) Dependent on Whether a gD Receptor or a gB Receptor Is Overexpressed
Differential Effects on Cell Fusion Activity of Mutations in Herpes Simplex Virus 1 Glycoprotein B (gB) Dependent on Whether a gD Receptor or a gB Receptor Is Overexpressed
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DOI：
10.1128/jvi.00087-09
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发表时间：
2009-08-01
影响因子：
5.4
通讯作者：
Spear, Patricia G.
中科院分区：
文献类型：
--
作者：
Fan, Qing;Lin, Erick;Spear, Patricia G.
单纯疱疹病毒（HSV）的糖蛋白B（gB）是病毒侵入和细胞融合所必需的四种糖蛋白之一。最近，配对免疫球蛋白样2型受体（PILR α）被鉴定为HSV 1型（HSV-1）gB的受体。PILR α和gD受体均显示参与HSV-1进入某些细胞类型。本研究的目的是确定gB中的插入突变是否对其与PILR α和gD受体nectin-1的功能具有不同的影响。先前描述的gB突变体和额外的新表征的突变体用于本研究中。我们发现，当PILR α过表达时，gB N末端和C末端附近的插入突变，尤其是胞外域中心区域的插入突变，比nectin-1过表达时降低了细胞融合活性。对于至少某些形式的gB，大多数插入减少了gB与PILR α的结合，但这种减少不一定与与PILR α的细胞融合活性的选择性降低相关。这些结果表明，相关突变靶向的区域对于PILR α的功能活性至关重要。他们还表明，尽管gB与gB受体的结合和gD与gD受体的结合可能是HSV诱导的细胞融合所需的，但这两种受体结合活性在触发融合活性方面可能具有不相等的权重，这取决于gB和gD受体的比率或其他因素。
Glycoprotein B (gB) of herpes simplex virus (HSV) is one of four glycoproteins essential for viral entry and cell fusion. Recently, paired immunoglobulin-like type 2 receptor (PILR alpha) was identified as a receptor for HSV type 1 (HSV-1) gB. Both PILR alpha and a gD receptor were shown to participate in HSV-1 entry into certain cell types. The purpose of this study was to determine whether insertional mutations in gB had differential effects on its function with PILR alpha and the gD receptor, nectin-1. Previously described gB mutants and additional newly characterized mutants were used in this study. We found that insertional mutations near the N terminus and C terminus of gB and especially in the central region of the ectodomain reduced cell fusion activity when PILR alpha was overexpressed much more than when nectin-1 was overexpressed. Most of the insertions reduced the binding of gB to PILR alpha, for at least some forms of gB, but this reduction did not necessarily correlate with the selective reduction in cell fusion activity with PILR alpha. These results suggest that the regions targeted by the relevant mutations are critical for functional activity with PILR alpha. They also suggest that, although both the binding of gB to a gB receptor and the binding of gD to a gD receptor may be required for HSV-induced cell fusion, the two receptor-binding activities may have unequal weights in triggering fusogenic activity, depending on the ratios of gB and gD receptors or other factors.