A derivative of platelet-derived growth factor receptor alpha binds to the trimer of human cytomegalovirus and inhibits entry into fibroblasts and endothelial cells.
Cora Stegmann,Daniel Hochdorfer,Diana Lieber,Narmadha Subramanian,Dagmar Stöhr,Kerstin Laib Sampaio,Christian Sinzger +6 more
TLDR
It is shown that soluble derivatives of the platelet-derived growth factor receptor alpha (PDGFR-alpha), a putative receptor of H CMV, can inhibit HCMV infection of various cell types and are hence promising candidates for the development of novel anti-HCMV therapies.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.read more
Citations
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Cytomegalovirus感染症 (ウイルス(特集))
TL;DR: CMV has an immunosuppressive effect, which can lead to an increased susceptibility to invasive bacterial and fungal disease as well as graftversus-host disease (GvHD).
Journal ArticleDOI
Pathogen at the Gates: Human Cytomegalovirus Entry and Cell Tropism
TL;DR: X-ray crystal structures for the proximal viral fusogen, glycoprotein B (gB), and for the pentameric gH/gL complex (pentamer) have been solved, and a novel virion gH complex consisting of gH bound to UL116 instead of gL was described, and findings supporting the existence of a stable complex between gH/.
Journal ArticleDOI
CD147 Promotes Entry of Pentamer-Expressing Human Cytomegalovirus into Epithelial and Endothelial Cells
Adam L. Vanarsdall,Sarah R. Pritchard,Todd W. Wisner,Jing Liu,Theodore S. Jardetzky,David C. Johnson +5 more
TL;DR: CD147 represents the first H CMV entry mediator that specifically functions to promote entry of pentamer-expressing HCMV into epithelial and endothelial cells, and will lead to a better understanding of HCMVs pathogenesis and have implications for the development of future therapeutics.
Journal ArticleDOI
Role of PDGF receptor-α during human cytomegalovirus entry into fibroblasts
TL;DR: Understanding is refined of the mechanism by which the cell-surface receptor tyrosine kinase, PDGF receptor-α, supports the entry of HCMV into fibroblasts, and several key determinants of H CMV tropism are clarified.
Journal ArticleDOI
The Human Cytomegalovirus Trimer and Pentamer Promote Sequential Steps in Entry into Epithelial and Endothelial Cells at Cell Surfaces and Endosomes.
TL;DR: A model in which both the trimer and pentamer are required for HCMV entry into epithelial and endothelial cells is supported, with trimer interacting with cell surface receptors other than PDGFR andpentamer acting later in the entry pathway to promote egress from endosomes.
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Journal ArticleDOI
Human Cytomegalovirus UL131-128 Genes Are Indispensable for Virus Growth in Endothelial Cells and Virus Transfer to Leukocytes
Gabriele Hahn,Maria Grazia Revello,Marco Patrone,Elena Percivalle,Giulia Campanini,Antonella Sarasini,Markus Wagner,Andrea Gallina,Gabriele Milanesi,Ulrich Koszinowski,Fausto Baldanti,Giuseppe Gerna +11 more
TL;DR: It is shown here that the UL131-128 gene locus of HCMV is indispensable for both productive infection of endothelial cells and transmission to leukocytes, and suggests that a common mechanism of virus transfer may be involved in both endothelial cell tropism and leukocyte transfer.
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