The Roles of Envelope Glycoprotein M in the Life Cycle of Some Alphaherpesviruses

Abstract

The envelope glycoprotein M (gM), a surface virion component conserved among alphaherpesviruses, is a multiple-transmembrane domain-containing glycoprotein with a complex N-linked oligosaccharide. The gM mediates a diverse range of functions during the viral life cycle. In this review, we summarize the biological features of gM, including its characterization and function in some specicial alphaherpesviruses. gM modulates the virus-induced membrane fusion during virus invasion, transports other proteins to the appropriate intracellular membranes for primary and secondary envelopment during virion assembly, and promotes egress of the virus. The gM can interact with various viral and cellular components, and the focus of recent research has also been on interactions related to gM. And we will discuss how gM participates in the life cycle of alphaherpesviruses.

Keywords: alphaherpesviruses; entry; fusion; glycoprotein M; the viral life cycles.

Figure 1

Predicted topology of herpes simplex virus 1 (HSV-1) glycoprotein M (gM). The topology of HSV-1 gM was predicted using the TMHMM transmembrane topology prediction server (http://www.cbs.dtu.dk/services/TMHMM/; Baines and Roizman, 1993; Striebinger et al., 2015; Striebinger et al., 2016).

Figure 2

The involvement of gM in the life cycle of HSV-1. (1) Viral genome is assembled into the capsid to form the nucleocapsid (Skepper et al., 2001); (2) The nucleocapsid acquires a small number of tegument proteins in the nucleus (Baines et al., 2007; Wills et al., 2009); (3) Immature virions budding in the inner nuclear membrane and enter the perinuclear space, meanwhile, gM is assembled into the primary envelope (Baines et al., 2007; Zhang et al., 2009); (4) The primary envelope is de-envelopment at the outer membrane and the naked nucleocapsid is released into the cytoplasm; (5) The naked nucleocapsid acquires a large number of tegument proteins in the cytoplasm (Johnson and Baines, 2011; Maringer et al., 2012); (6) gD, gH, and gL located on the surface of cell membrane were internalized by gM and relocated to Golgi apparatus (Ren et al., 2012); (7) gN and gM located in the endoplasmic reticulum (ER) form complex and matures, and then transfer to Golgi apparatus (Graul et al., 2019); (8) The nucleocapsid is wrapped by tegument proteins and obtained the ultimate envelope at the Golgi apparatus (Turcotte et al., 2005); (9)–(10) The vesicles derive from Golgi apparatus and wrap the enveloped virions and transported them to the cell membrane (Sugimoto et al., 2008); (11) Progeny virions released by exocytosis at cell membrane (Turcotte et al., 2005; Johnson and Baines, 2011); and (12) gM antagonized the tetherin and virions were successfully released (Blasius et al., 2006).