title: A derivative of platelet-derived growth factor receptor alpha binds to the trimer of human cytomegalovirus and inhibits entry into fibroblasts and endothelial cells.
abstract: Human cytomegalovirus (HCMV) is a widely distributed herpesvirus that causes significant morbidity in immunocompromised hosts. Inhibitors of viral DNA replication are available, but adverse effects limit their use. Alternative antiviral strategies may include inhibition of entry. We show that soluble derivatives of the platelet-derived growth factor receptor alpha (PDGFR-alpha), a putative receptor of HCMV, can inhibit HCMV infection of various cell types. A PDGFR-alpha-Fc fusion protein binds to and neutralizes cell-free virus particles at an EC50 of 10-30 ng/ml. Treatment of particles reduced both attachment to and fusion with cells. In line with the latter, PDGFR-alpha-Fc was also effective when applied postattachment. A peptide scan of the extracellular domain of PDGFR-alpha identified a 40mer peptide that inhibits infection at an EC50 of 1-2 nmol/ml. Both, peptide and fusion protein, were effective against various HCMV strains and are hence promising candidates for the development of novel anti-HCMV therapies.
authors.affiliation: Institute of Virology, University of Ulm, Ulm, Germany.
authors.forename: Cora
authors.identifier: http://orcid.org/0000-0003-4408-4026
authors.initials: C
authors.lastname: Stegmann
authors.affiliation: Institute of Virology, University of Ulm, Ulm, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hochdorfer
authors.affiliation: Institute of Virology, University of Ulm, Ulm, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Lieber
authors.affiliation: Institute of Virology, University of Ulm, Ulm, Germany.
authors.forename: Narmadha
authors.initials: N
authors.lastname: Subramanian
authors.affiliation: Institute of Virology, University of Ulm, Ulm, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Stöhr
authors.affiliation: Institute of Virology, University of Ulm, Ulm, Germany.
authors.forename: Kerstin
authors.identifier: http://orcid.org/0000-0003-1124-9664
authors.initials: K
authors.lastname: Laib Sampaio
authors.affiliation: Institute of Virology, University of Ulm, Ulm, Germany.
authors.forename: Christian
authors.identifier: http://orcid.org/0000-0002-9282-1783
authors.initials: C
authors.lastname: Sinzger
mesh_terms: D000998:Antiviral Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D003587:Cytomegalovirus / Q000187:drug effects* / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000628:therapy* / Q000821:virology; D042783:Endothelial Cells / Q000821:virology; D005347:Fibroblasts / Q000821:virology; D006801:Humans; D010455:Peptides / Q000302:isolation & purification / Q000494:pharmacology*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D014771:Virion; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D010455:Peptides; D011993:Recombinant Fusion Proteins; D020796:Receptor, Platelet-Derived Growth Factor alpha