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Engineered receptors for human cytomegalovirus that are orthogonal to normal human biology

ABSTRACT: A trimeric glycoprotein complex on the surface of human cytomegalovirus (CMV) binds to platelet-derived growth factor (PDGF) receptor α (PDGFRα) to mediate host cell recognition and fusion of the viral and cellular membranes. Soluble PDGFRα potently neutralizes CMV in tissue culture, and its potential use as an antiviral therapeutic has the benefit that any escape mutants will likely be attenuated. However, PDGFRα binds multiple PDGF ligands in the human body as part of developmental programs in embryogenesis and continuing through adulthood. Any therapies with soluble receptor therefore come with serious efficacy and safety concerns, especially for the treatment of congenital CMV. Soluble virus receptors that are orthogonal to human biology would reduce safety and efficacy concerns. This engineering problem is solved by deep mutational scanning on the D2-D3 domains of PDGFRα to identify variants that maintain interactions with the CMV glycoprotein trimer in the presence of competing PDGF ligands.

ORGANISM(S): Homo sapiens

PROVIDER: GSE138169 | GEO | 2020/06/01

REPOSITORIES: GEO

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