Pseudorabies virus glycoprotein B can be used to carry foot and mouth disease antigens in DNA vaccination of pigs

Dory, Daniel; Remond, Michèle; Beven, Véronique; Cariolet, Roland; Backović, Marija; Zientara, Stéphan; Jestin, André

doi:10.1016/j.antiviral.2008.11.005

Cited by 7 publications

(2 citation statements)

References 40 publications

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“…The low-resolution structure obtained for the full-length HSV-1 gB in a conformation distinct from the postfusion conformation localizes domain IV to the interior of the spike (30), implying that a large movement occurs during the conformational change. Insertion of a foot-and-mouth disease virus (FMDV) epitope in PrV gB domain IV, right after the residue Arg685, resulted in high titers of neutralizing antibodies against FMDV (77), suggesting that at least some of the antigenic determinants on PrV gB domain IV are presented at the surface when the protein is expressed in its prefusion form. It is also possible, however, that the epitope is available because a fraction of gB at the virion surface may have adopted the postfusion conformation.…”

Section: Discussionmentioning

confidence: 99%

Structure-Function Dissection of Pseudorabies Virus Glycoprotein B Fusion Loops

Vallbracht

Brun

Tassinari

et al. 2018

J Virol

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Conserved across the family Herpesviridae, glycoprotein B (gB) is responsible for driving fusion of the viral envelope with the host cell membrane for entry upon receptor binding and activation by the viral gH/gL complex. Although crystal structures of the gB ectodomains of several herpesviruses have been reported, the membrane fusion mechanism has remained elusive. Here, we report the X-ray structure of the pseudorabies virus (PrV) gB ectodomain, revealing a typical class III postfusion trimer that binds membranes via its fusion loops (FLs) in a cholesterol-dependent manner. Mutagenesis of FL residues allowed us to dissect those interacting with distinct subregions of the lipid bilayer and their roles in membrane interactions. We tested 15 gB variants for the ability to bind to liposomes and further investigated a subset of them in functional assays. We found that PrV gB FL residues Trp187, Tyr192, Phe275, and Tyr276, which were essential for liposome binding and for fusion in cellular and viral contexts, form a continuous hydrophobic patch at the gB trimer surface. Together with results reported for other alphaherpesvirus gBs, our data suggest a model in which Phe275 from the tip of FL2 protrudes deeper into the hydrocarbon core of the lipid bilayer, while the side chains of Trp187, Tyr192, and Tyr276 form a rim that inserts into the more superficial interfacial region of the membrane to catalyze the fusion process. Comparative analysis with gBs from beta- and gamma-herpesviruses suggests that this membrane interaction model is valid for gBs from all herpesviruses. IMPORTANCE Herpesviruses are common human and animal pathogens that infect cells by entering via fusion of viral and cellular membranes. Central to the membrane fusion event is glycoprotein B (gB), which is the most conserved envelope protein across the herpesvirus family. Like other viral fusion proteins, gB anchors itself in the target membrane via two polypeptide segments called fusion loops (FLs). The molecular details of how gB FLs insert into the lipid bilayer have not been described. Here, we provide structural and functional data regarding key FL residues of gB from pseudorabies virus, a porcine herpesvirus of veterinary concern, which allows us to propose, for the first time, a molecular model to understand how the initial interactions by gBs from all herpesviruses with target membranes are established.

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Section: Discussionmentioning

confidence: 99%

Structure-Function Dissection of Pseudorabies Virus Glycoprotein B Fusion Loops

Vallbracht

Brun

Tassinari

et al. 2018

J Virol

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“…There are 10 glycoproteins encoded by PRV, which are divided into two groups (essential or non-essential glycoproteins) according to the degree to which viral replication depends on them [ 13 , 14 ]. The glycoprotein B (gB) plays a crucial role in membrane fusion during infection and in spreading viruses from cell to cell [ 15 , 16 , 17 ]. A major glycoprotein encoded by the glycoprotein C gene mediates the attachment of PRV to target cells through heparin-binding domains [ 11 , 18 , 19 , 20 ].…”

Section: The Biological Characteristics Of Prvmentioning

confidence: 99%

Recombinant Pseudorabies Virus Usage in Vaccine Development against Swine Infectious Disease

Zhou

Abid

Cao

et al. 2023

Viruses

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Pseudorabies virus (PRV) is the pathogen of pseudorabies (PR), which belongs to the alpha herpesvirus subfamily with a double stranded DNA genome encoding approximately 70 proteins. PRV has many non-essential regions for replication, has a strong capacity to accommodate foreign genes, and more areas for genetic modification. PRV is an ideal vaccine vector, and multivalent live virus-vectored vaccines can be developed using the gene-deleted PRV. The immune system continues to be stimulated by the gene-deleted PRVs and maintain a long immunity lasting more than 4 months. Here, we provide a brief overview of the biology of PRV, recombinant PRV construction methodology, the technology platform for efficiently constructing recombinant PRV, and the applications of recombinant PRV in vaccine development. This review summarizes the latest information on PRV usage in vaccine development against swine infectious diseases, and it offers novel perspectives for advancing preventive medicine through vaccinology.

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