Common characteristics and unique features: A comparison of the fusion machinery of the alphaherpesviruses Pseudorabies virus and Herpes simplex virus

Influence of N-glycosylation on Expression and Function of Pseudorabies Virus Glycoprotein gB

“…Early studies revealed that gB cleavage occurs in the Golgi apparatus after gB oligomerization in the ER [45]. Herpesvirus gB is believed to undergo extensive conformational changes for fusion and is reported to transit from a (predicted) trimeric pre-to a trimeric post-fusion form [5]. Only recently, the pre-fusion structure of HSV-1 gB was reported [24].…”

“…Whereas many enveloped viruses encode a single but multifunctional glycoprotein (g) for host-cell receptor-binding and membrane fusion [4], herpesviruses utilize a multiprotein machinery to mediate these processes. The so-called "core-fusion machinery" which is conserved in all herpesviruses is formed by gB, the bona fide fusion protein, and the heterodimeric complex of the membrane-bound gH and anchorless gL (gH/gL) [5]. In addition to the core-fusion machinery, herpesviruses require the assistance of nonconserved subgroup-specific receptor-binding proteins such as gD of the Alphaherpesvirinae for entry [6][7][8].…”

“…A conformational change in receptor-bound gD is proposed to allow its crosstalk with gH/gL, possibly by direct interaction between their ectodomains [14]. The gH/gL complex is believed to function as a fusion regulator and, upon triggering, is thought to activate gB, the sole fusion executor [5,9,11,15]. Although the exact molecular mechanism of gB fusion activation by gH/gL is unclear, direct interactions between the respective ectodomains and/or cytoplasmic domains have been reported to be essential for fusion activation [16,17].…”

“…During the fusogenic conformational change, gB exposes two internal fusion loops that interact with the target membrane [18]. The subsequent fold-back process into the energetically more favorable post-fusion conformation juxtaposes the viral and cellular membranes, ultimately leading to their fusion [5].…”

“…gB is the most highly conserved component of the herpesvirus fusion machinery and exhibits around 50% amino acid (aa) sequence identity within each subfamily [5]. High-resolution crystal structures of the stable post-fusion state have been determined for gB ectodomains of five different herpesviruses, including PrV [18,19], HSV-1 [20], and VZV [21], all revealing rod-shaped trimers which are composed of five domains (DI-V) per protomer (Figure 1).…”