Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
J Gen Virol. 2012 Feb;93(Pt 2):319-329. doi: 10.1099/vir.0.035444-0. Epub 2011 Oct 19.
Herpes simplex virus type 1 glycoprotein M (gM) is a type III membrane protein conserved throughout the family Herpesviridae. However, despite this conservation, gM is classed as a non-essential protein in most alphaherpesviruses. Previous data have suggested that gM is involved in secondary envelopment, although how gM functions in this process is unknown. Using transfection-based assays, we have previously shown that gM is able to mediate the internalization and subcellular targeting of other viral envelope proteins, suggesting a possible role for gM in localizing herpesvirus envelope proteins to sites of secondary envelopment. To investigate the role of gM in infected cells, we have now analysed viral envelope protein localization and virion incorporation in cells infected with a gM-deletion virus or its revertant. In the absence of gM expression, we observed a substantial inhibition of glycoprotein H-L (gH-L) internalization from the surface of infected cells. Although deletion of gM does not affect expression of gH and gL, virions assembled in the absence of gM demonstrated significantly reduced levels of gH-L, correlating with defects of the gM-negative virus in entry and cell-to-cell spread. These data suggest an important role of gM in mediating the specific internalization and efficient targeting of gH-L to sites of secondary envelopment in infected cells.
单纯疱疹病毒 1 型糖蛋白 M（gM）是一种 III 型膜蛋白，在疱疹病毒家族中广泛保守。然而，尽管存在这种保守性，gM 在大多数α疱疹病毒中被归类为非必需蛋白。先前的数据表明，gM 参与了次级包膜的形成，尽管 gM 在这个过程中的作用尚不清楚。我们之前通过转染实验表明，gM 能够介导其他病毒包膜蛋白的内化和亚细胞靶向，这表明 gM 可能在将疱疹病毒包膜蛋白定位到次级包膜形成部位方面发挥作用。为了研究 gM 在感染细胞中的作用，我们现在分析了感染 gM 缺失病毒或其回复病毒的细胞中病毒包膜蛋白的定位和病毒粒子的掺入。在没有 gM 表达的情况下，我们观察到从感染细胞表面内化糖蛋白 H-L（gH-L）的显著抑制。尽管 gM 的缺失不影响 gH 和 gL 的表达，但在没有 gM 的情况下组装的病毒粒子显示出 gH-L 的水平显著降低，这与 gM 阴性病毒在进入和细胞间传播中的缺陷相关。这些数据表明 gM 在介导 gH-L 特异性内化和有效靶向感染细胞中的次级包膜形成部位方面发挥重要作用。
