Novel heparan sulfate-binding peptides for blocking herpesvirus entry

Pranay Dogra, Emily Martin, Angela Williams, Raphael L. Richardson, James S. Foster, Nicole Hackenback, Stephen Kennel, Tim E. Sparer, Jonathan Wall

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 broadspectrum 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.

Original languageEnglish (US)
Article numbere0126239
JournalPLoS ONE
Volume10
Issue number5
DOIs
StatePublished - May 18 2015
Externally publishedYes

Fingerprint

Heparitin Sulfate
Herpesviridae
Heparan Sulfate Proteoglycans
peptides
Viruses
Peptides
Human herpesvirus 5
Adsorption
Infection
proteoglycans
infection
Virus Diseases
Cytomegalovirus
adsorption
viruses
Herpesviridae Infections
Aptitude
Human Herpesvirus 2
Cytomegalovirus Infections
Human Herpesvirus 1

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Dogra, P., Martin, E., Williams, A., Richardson, R. L., Foster, J. S., Hackenback, N., ... Wall, J. (2015). Novel heparan sulfate-binding peptides for blocking herpesvirus entry. PLoS ONE, 10(5), [e0126239]. https://doi.org/10.1371/journal.pone.0126239

Novel heparan sulfate-binding peptides for blocking herpesvirus entry. / Dogra, Pranay; Martin, Emily; Williams, Angela; Richardson, Raphael L.; Foster, James S.; Hackenback, Nicole; Kennel, Stephen; Sparer, Tim E.; Wall, Jonathan.

In: PLoS ONE, Vol. 10, No. 5, e0126239, 18.05.2015.

Research output: Contribution to journalArticle

Dogra, P, Martin, E, Williams, A, Richardson, RL, Foster, JS, Hackenback, N, Kennel, S, Sparer, TE & Wall, J 2015, 'Novel heparan sulfate-binding peptides for blocking herpesvirus entry', PLoS ONE, vol. 10, no. 5, e0126239. https://doi.org/10.1371/journal.pone.0126239
Dogra P, Martin E, Williams A, Richardson RL, Foster JS, Hackenback N et al. Novel heparan sulfate-binding peptides for blocking herpesvirus entry. PLoS ONE. 2015 May 18;10(5). e0126239. https://doi.org/10.1371/journal.pone.0126239
Dogra, Pranay ; Martin, Emily ; Williams, Angela ; Richardson, Raphael L. ; Foster, James S. ; Hackenback, Nicole ; Kennel, Stephen ; Sparer, Tim E. ; Wall, Jonathan. / Novel heparan sulfate-binding peptides for blocking herpesvirus entry. In: PLoS ONE. 2015 ; Vol. 10, No. 5.
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