A Derivative of Platelet-derived Growth Factor Receptor Alpha Binds to the Trimer of Human Cytomegalovirus and Inhibits Entry into Fibroblasts and Endothelial Cells

Overview

Journal PLoS Pathog

Specialty Microbiology

Date 2017 Apr 14

PMID 28403220

Citations 54

Authors

Cora Stegmann

Daniel Hochdorfer

Diana Lieber

Narmadha Subramanian

Dagmar Stohr

Kerstin Laib Sampaio

Christian Sinzger

Affiliations

Soon will be listed here.

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.

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