The Engineering of a Novel Ligand in gH Confers to HSV an Expanded Tropism Independent of gD Activation by Its Receptors

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To enter cells, all herpesviruses use the core fusion glycoproteins gH/gL and gB, in addition to species-specific glycoproteins responsible for specific tropism, etc. In HSV, the additional glycoprotein is the essential gD. We engineered in gH a heterologous ligand to the HER2 cancer receptor. The recombinant viruses entered cells through HER2, independently of gD activation by its receptors, or despite deletion of key residues that are part of the receptors’ binding sites in gD. The ligand activated gH in cis. Cumulatively, the receptor-binding and activating functions of gD were no longer essential and were replaced by the heterologous ligand in gH. Relevance to translational medicine rests in the fact that gH can serve as a tool to retarget HSV tropism to cancer-specific receptors. This expands the toolkit for the design of fully-virulent oncolytic-HSVs.

Vyšlo v časopise: The Engineering of a Novel Ligand in gH Confers to HSV an Expanded Tropism Independent of gD Activation by Its Receptors. PLoS Pathog 11(5): e32767. doi:10.1371/journal.ppat.1004907
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004907

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