Source Publication
PLOS One
Document Type
Article
Publication Date
5-18-2015
DOI
10.1371/journal.pone.0126239
Abstract
Human cytomegalovirus (HCMV) infection can lead to congenital hearing loss and mental retardation. Upon immune suppression, reactivation of latent HCMV or primary infection increases morbidity in cancer, transplantation, and late stage AIDS patients. Current treatments include nucleoside analogues, which have significant toxicities limiting their usefulness. In this study we screened a panel of synthetic heparin-binding peptides for their ability to prevent CMV infection in vitro. A peptide designated, p5+14 exhibited ~ 90% reduction in murine CMV (MCMV) infection. Because negatively charged, cell-surface heparan sulfate proteoglycans (HSPGs), serve as the attachment receptor during the adsorption phase of the CMV infection cycle, we hypothesized that p5+14 effectively competes for CMV adsorption to the cell surface resulting in the reduction in infection. Positively charged Lys residues were required for peptide binding to cell-surface HSPGs and reducing viral infection. We show that this inhibition was not due to a direct neutralizing effect on the virus itself and that the peptide blocked adsorption of the virus. The peptide also inhibited infection of other herpesviruses: HCMV and herpes simplex virus 1 and 2 in vitro, demonstrating it has broad-spectrum antiviral activity. Therefore, this peptide may offer an adjunct therapy for the treatment of herpes viral infections and other viruses that use HSPGs for entry.
Recommended Citation
Dogra P, Martin EB, Williams A, Richardson RL, Foster JS, Hackenback N, et al. (2015) Novel Heparan Sulfate-Binding Peptides for Blocking Herpesvirus Entry. PLoS ONE 10(5): e0126239. doi:10.1371/journal.pone.0126239
Submission Type
Publisher's Version
Comments
This article was published openly thanks to the University of Tennessee Open Publishing Support Fund.
Licensed under a Creative Commons Attribution 4.0 International license.