ArticlePLoS pathogens2015
The Engineering of a Novel Ligand in gH Confers to HSV an Expanded Tropism Independent of gD Activation by Its Receptors.
Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 33 citations in OpenAlex.
- Engineering HSV-1 for oncolytic therapy: From molecular entry mechanisms to retargeting strategies.Genes & diseases · 2026Review
- Development of a novel, high-efficacy oncolytic herpes simplex virus type 1 platform equipped with two distinct retargeting modalities.Molecular therapy. Oncology · 2024Article
- TheraVision: Engineering platform technology for the development of oncolytic viruses based on herpes simplex virus type 1.Molecular therapy. Oncology · 2024Article
- Article
- Oncolytic virotherapy evolved into the fourth generation as tumor immunotherapy.Journal of translational medicine · 2023Review
- Innovative retargeted oncolytic herpesvirus against nectin4-positive cancers.Frontiers in molecular biosciences · 2023Article
- Towards a Precision Medicine Approach and In Situ Vaccination against Prostate Cancer by PSMA-Retargeted oHSV.Viruses · 2021Article
- Article
- Immunotherapeutic Efficacy of Retargeted oHSVs Designed for Propagation in an Ad Hoc Cell Line.Cancers · 2021Review
- Herpes Simplex Virus Oncolytic Immunovirotherapy: The Blossoming Branch of Multimodal Therapy.International journal of molecular sciences · 2020Review
- An oncolytic herpesvirus expressing E-cadherin improves survival in mouse models of glioblastoma.Nature biotechnology · 2018Article
- Oncolytic herpes simplex virus tumor targeting and neutralization escape by engineering viral envelope glycoproteins.Drug delivery · 2018Review
- Recombinant viruses with other anti-cancer therapeutics: a step towards advancement of oncolytic virotherapy.Cancer gene therapy · 2018Review
- A fully-virulent retargeted oncolytic HSV armed with IL-12 elicits local immunity and vaccine therapy towards distant tumors.PLoS pathogens · 2018Article
- HSV as A Platform for the Generation of Retargeted, Armed, and Reporter-Expressing Oncolytic Viruses.Viruses · 2018Article
- Dual Ligand Insertion in gB and gD of Oncolytic Herpes Simplex Viruses for Retargeting to a Producer Vero Cell Line and to Cancer Cells.Journal of virology · 2018Article
- Simultaneous Insertion of Two Ligands in gD for Cultivation of Oncolytic Herpes Simplex Viruses in Noncancer Cells and Retargeting to Cancer Receptors.Journal of virology · 2018Article
- First Impressions-the Potential of Altering Initial Host-Virus Interactions for Rational Design of Herpesvirus Vaccine Vectors.Current clinical microbiology reports · 2018Article
- Herpesviral vectors and their application in oncolytic therapy, vaccination, and gene transfer.Virus genes · 2017Review
- A Strategy for Cultivation of Retargeted Oncolytic Herpes Simplex Viruses in Non-cancer Cells.Journal of virology · 2017Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Herpes simplex virus (HSV) enters cells by means of four essential glycoproteins - gD, gH/gL, gB, activated in a cascade fashion by gD binding to one of its receptors, nectin1 and HVEM. We report that the engineering in gH of a heterologous ligand - a single-chain antibody (scFv) to the cancer-specific HER2 receptor - expands the HSV tropism to cells which express HER2 as the sole receptor. The significance of this finding is twofold. It impacts on our understanding of HSV entry mechanism and the design of retargeted oncolytic-HSVs. Specifically, entry of the recombinant viruses carrying the scFv-HER2-gH chimera into HER2+ cells occurred in the absence of gD receptors, or upon deletion of key residues in gD that constitute the nectin1/HVEM binding sites. In essence, the scFv in gH substituted for gD-mediated activation and rendered a functional gD non-essential for entry via HER2. The activation of the gH moiety in the chimera was carried out by the scFv in cis, not in trans as it occurs with wt-gD. With respect to the design of oncolytic-HSVs, previous retargeting strategies were based exclusively on insertion in gD of ligands to cancer-specific receptors. The current findings show that (i) gH accepts a heterologous ligand. The viruses retargeted via gH (ii) do not require the gD-dependent activation, and (iii) replicate and kill cells at high efficiency. Thus, gH represents an additional tool for the design of fully-virulent oncolytic-HSVs retargeted to cancer receptors and detargeted from gD receptors.
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