A derivative of platelet-derived growth factor receptor alpha binds to the trimer of human cytomegalovirus and inhibits entry into fibroblasts and endothelial cells

PLoS Pathogens

Diana Lieber¹  Dagmar Stöhr¹  Narmadha Subramanian¹  Daniel Hochdorfer¹  Cora Stegmann¹  Christian Sinzger¹  Kerstin Laib Sampaio¹ 

[1] Institute of Virology, University of Ulm, Ulm, Germany

关键词: Endothelial cells;    Fibroblasts;    Small interfering RNAs;    Virions;    Cell staining;    Cell binding;    Antibodies;    Human cytomegalovirus;   

DOI  :  10.1371/journal.ppat.1006273

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY