Structural basis of nectin-1 recognition by pseudorabies virus glycoprotein D

Abstract

An early and yet indispensable step in the alphaherpesvirus infection is the engagement of host receptors by the viral envelope glycoprotein D (gD). Of the thus-far identified gD receptors, nectin-1 is likely the most effective in terms of its wide usage by multiple alphaherpesviruses for cell entry. The molecular basis of nectin-1 recognition by the gD protein is therefore an interesting scientific question in the alphaherpesvirus field. Previous studies focused on the herpes simplex virus (HSV) of the Simplexvirus genus, for which both the free gD structure and the gD/nectin-1 complex structure were reported at high resolutions. The structural and functional features of other alphaherpesviral gDs, however, remain poorly characterized. In the current study, we systematically studied the characteristics of nectin-1 binding by the gD of a Varicellovirus genus member, the pseudorabies virus (PRV). We first showed that PRV infects host cells via both human and swine nectin-1, and that its gD exhibits similar binding affinities for nectin-1 of the two species. Furthermore, we demonstrated that removal of the PRV gD membrane-proximal residues could significantly increase its affinity for the receptor binding. The structures of PRV gD in the free and the nectin-1-bound states were then solved, revealing a similar overall 3D fold as well as a homologous nectin-1 binding mode to its HSV counterpart. However, several unique features were observed at the binding interface of PRV gD, enabling the viral ligand to utilize different gD residues (from those of HSV) for nectin-1 engagement. These observed binding characteristics were further verified by the mutagenesis study using the key-residue mutants of nectin-1. The structural and functional data obtained in this study, therefore, provide the basis of receptor recognition by PRV gD.

Molecular basis of binding between the global post-transcriptional regulator CsrA and the T3SS chaperone CesT

“…1c ). Despite of the altered binding kinetics (which is commonly observed in the ligand/receptor interactions when the interface residues are mutated 34 – 36 ), the affinity between Re-CsrA and CesT, which is calculated to be ~151 nM, is in good accordance with that observed for the WT proteins. The recombinant protein therefore represents a good candidate for structural investigations on the molecular basis of CesT/CsrA recognition.…”

Human encephalitis complicated with bilateral acute retinal necrosis associated with pseudorabies virus infection: A case report

“…However, in 2017, Li et al reported a case of endophthalmitis caused by PRV, which was highly homologous to three highly pathogenic PRV variants in China. Moreover, they discovered that PRV could interact with both human and swine cellular receptor nectin-1 via the envelope glycoprotein D (gD) on the viral surface (Li et al, 2017). This discovery might explain the possibility of zoonosis caused by PRV variants and stresses the necessity for researchers and workers in the breeding industry to increase awareness of self-protection.…”

Zinc in Wound Healing Modulation

“…Absence of zinc, via chelators, compromises NETosis [ 60 ]. The contents of NETs include heterodimeric proteins known as calprotectin [ 61 ]. Calprotectin is able to bind and sequester zinc ions [ 62 ].…”