Bovine single chain Fv antibody inhibits bovine herpesvirus-1 infectivity by targeting viral glycoprotein D

2017 ◽  
Vol 101 (23-24) ◽  
pp. 8331-8344 ◽  
Author(s):  
Jian Xu ◽  
Jing Wu ◽  
Bo Jiang ◽  
Houjun He ◽  
Xixi Zhang ◽  
...  
Keyword(s):  
Bovine Herpesvirus ◽  
Glycoprotein D ◽  
Single Chain ◽  
Viral Glycoprotein ◽  
Bovine Herpesvirus 1 ◽  
Single Chain Fv ◽  
Fv Antibody ◽  
Herpesvirus 1 ◽  
Single Chain Fv Antibody

scholarly journals Crystal structure of bovine herpesvirus 1 glycoprotein D bound to nectin-1 reveals the basis for its low-affinity binding to the receptor

2020 ◽  
Vol 6 (20) ◽  
pp. eaba5147
Author(s):  
Dan Yue ◽  
Zhujun Chen ◽  
Fanli Yang ◽  
Fei Ye ◽  
Sheng Lin ◽  
...  
Keyword(s):  
Functional Data ◽  
Bovine Herpesvirus ◽  
Binding Mode ◽  
Cell Entry ◽  
Glycoprotein D ◽  
Viral Glycoprotein ◽  
Bovine Herpesvirus 1 ◽  
Receptor Recognition ◽  
Large Conformational Change ◽  
Herpesvirus 1

Bovine herpesvirus 1 (BHV-1) has received increasing attention for its potential oncolytic applications. BHV-1 recognizes nectin-1 for cell entry via viral glycoprotein D (gD) but represents a low-affinity nectin-1 binding virus. The molecular basis underlying this low receptor-binding affinity, however, remains unknown. Here, the crystal structures of BHV-1 gD in the free and nectin-1–bound forms are presented. While showing an overall resembled nectin-1 binding mode to other alphaherpesvirus gDs, BHV-1 gD has a unique G-strand/α2-helix interloop that disturbs gD/nectin-1 interactions. Residue R188 residing in this loop is observed to otherwise cause strong steric hindrance with the bound receptor, making a large conformational change of the loop a prerequisite for nectin-1 engagement. Subsequently, substitution of R188 with glycine markedly enhances the affinity of the BHV-1-gD/nectin-1 interaction (by about fivefold). These structural and functional data delineate the receptor-recognition basis for BHV-1, which might facilitate BHV-1–based oncolytic design in the future.

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