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.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Stegmann C,Hochdorfer D,Lieber D,Subramanian N,Stöhr D,Laib Sampaio K,Sinzger C

doi

10.1371/journal.ppat.1006273

subject

Has Abstract

pub_date

2017-04-12 00:00:00

pages

e1006273

issue

4

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-16-01778

journal_volume

13

pub_type

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