Entry of Alphaherpesviruses

Abstract

Alphaherpesviruses are enveloped viruses that enter cells by fusing the viral membrane with a host cell membrane, either within an endocytic vesicle or at the plasma membrane. This entry event is mediated by a set of essential entry glycoproteins, including glycoprotein D (gD), gHgL, and gB. gHgL and gB are conserved among herpesviruses, but gD is unique to the alphaherpesviruses and is not encoded by all alphaherpesviruses. gD is a receptor-binding protein, the heterodimer gHgL serves as a fusion regulator, and gB is a class III viral fusion protein. Sequential interactions among these glycoproteins are thought to trigger the virus to fuse at the right place and time. Structural studies of these glycoproteins from multiple alphaherpesviruses has enabled the design and interpretation of functional studies. The structures of gD in a receptorbound and in an unliganded form reveal a conformational change in the C terminus of the gD ectodomain upon receptor binding that may serve as a signal for fusion. By mapping neutralizing antibodies to the gHgL structures and constructing interspecies chimeric forms of gHgL, interaction sites for both gD and gB on gHgL have been proposed. A comparison of the postfusion caister.com/cimb 63 Curr. Issues Mol. Biol. Vol. 41 Entry of AlphaherpesvirusesCairns and Connolly structure of gB and an alternative conformation of gB visualized using cryoelectron tomography suggests that gB undergoes substantial refolding to execute membrane fusion. Although these structures have provided excellent insights into the entry mechanism, many questions remain about how these viruses coordinate the interactions and conformational changes required for entry.

In-vitroreconstitution of Herpes Simplex Virus 1 fusion identifies low pH as a fusion co-trigger

“…7A ). This suggests that the fusion mechanism is the same regardless of the receptor, which is consistent with the current model [reviewed in (10, 14, 15)]. Therefore, we hypothesize that the differences in fusion extent in the presence of HVEM200t-His 8 or nectin345t-His 8 are due to differences in fusion efficiency.…”

“…In HSV-1, entry-associated functions are distributed across four viral glycoproteins: gD, gH, gL, and gB [reviewed in (10–12)]. According to the current model, these four viral glycoproteins orchestrate membrane fusion through a sequential activation process termed regulatory cascade (13) [reviewed in (10, 14, 15)]. First, the receptor-binding glycoprotein, gD, binds one of its three cognate receptors on the surface of the host cell and undergoes a conformational change, enabling it to bind and activate the gH/gL complex.…”

Multiple Sites on Glycoprotein H (gH) Functionally Interact with the gB Fusion Protein to Promote Fusion during Herpes Simplex Virus (HSV) Entry

“…We concluded that the gH-S830N mutation contributed to enhanced entry using the same reasoning as for the gH-H789Y mutation above. gH-S830 maps to the short gH CT (residues 825–838) that is essential for WT levels of fusion ( 1 , 2 , 38 ).…”

Membrane fusion, potential threats, and natural antiviral drugs of pseudorabies virus

“…Human nectin-1 shares 96% amino acid identity with porcine nectin-1. Although PrV gD exhibits similar affinity for both human and porcine nectin-1 [ 26 , 28 , 29 ], the PrV gD binding affinity for human nectin-1 is ten-fold higher than that of HSV-1 gD [ 26 , 27 ], which may explain human PrV infection. Despite the low amino acid homology of PrV and HSV gDs, most of their secondary structure elements are similar.…”