Mapping sites of herpes simplex virus type 1 glycoprotein D that permit insertions and impact gD and gB receptors usage
نویسندگان
چکیده
Glycoprotein D (gD) of herpes simplex virus type 1 (HSV-1) is one of four glycoproteins essential for HSV entry and cell fusion. The purpose of this study was to determine the plasticity of gD to tolerate insertion or deletion mutations and to construct an oncolytic HSV-1 that utilizes the disialoganglioside GD2 as a HSV-1 entry receptor. We found that the N-terminus of gD tolerates long insertions, whereas residues adjacent to the gD Ig-like V-type core tolerated shorter insertions (up to 15 amino acids), but not greater than 60 amino acids. Recombinant HSV-1 containing the ch14.18 single chain variable fragment (scFv) at the N-terminus of gD failed to mediate entry, even though the ch14.18 scFv-gD chimera Fc bound to neuroblastoma cells expressing GD2. Finally, we found that hyperfusogenic gB mutants enhanced fusion to a greater degree with the gB receptor the paired immunoglobulin-like type 2 receptor alpha (PILRα) than with gD receptors HVEM and nectin-1. Hyperfusogenic gB could restore the fusion function with PILRα when a gD constructed contained only the "profusion domain" (PFD), suggesting the hyperfusogenic form of gB may regulate fusion of PILRα via a novel mechanism through gH/gL and the gD PFD.
منابع مشابه
Expression of the Herpes Simplex Virus Type 2 Glycoprotein D in Baculovirus Expression System and Evaluation of Its Immunogenicity in Guinea Pigs
Background: Herpes simplex virus type 2 (HSV-2) is highly prevalent and major cause of genital herpes in humans. The life-long nature of infection and the increasing prevalence of genital herpes imply that vaccination is the best strategy for controlling the spread of infection and limiting HSV disease. HSV glycoprotein D (gD) is one of the most important viral immunogen which has an essential ...
متن کاملConstruction of an Eukaryotic Expression Vector Encoding Herpes Simplex Virus Type 2 Glycoprotein D and In Vitro Expression of the Desired Protein
To construct of an eukaryotic expression vector encoding herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2), an Iranian isolate of HSV-2 was propagated in HeLa cell line and its DNA was extracted and used as template in polymerase chain reactions (PCR), to amplify gD2 gene. Primers were designed and the restriction enzyme sites for EcoRI and XhoI were considered at their 5′ ends respectiv...
متن کاملDetection of Herpes Simplex Virus Antibodies Using the Whole Virus and Recombinant gD
Background and Aims: Herpes simplex virus type 1 (HSV1) remains a potentially serious health problem world wide. All infected people, including asymptomatic ones, are potential sources for virus transmission. Virus envelope contains at least 13 glycoproteins, which glycoprotein D is the major target of immune responses. The aim of this study was development of a specific method that is a more...
متن کاملImmunogenicity and Efficacy of Baculovirus Derived Glycoprotein D of Herpes Simplex Virus Type-I in Mice
متن کامل
PILRα Is a Herpes Simplex Virus-1 Entry Coreceptor That Associates with Glycoprotein B
Glycoprotein B (gB) is one of the essential components for infection by herpes simplex virus-1 (HSV-1). Although several cellular receptors that associate with glycoprotein D (gD), such as herpes virus entry mediator (HVEM) and Nectin-1, have been identified, specific molecules that mediate HSV-1 infection by associating with gB have not been elucidated. Here, we found that paired immunoglobuli...
متن کامل