June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
A cyclic anti-heparan sulfate peptide provides protection against primary and recurrent herpes simplex virus-1 (HSV-1) infection of the cornea
Author Affiliations & Notes
  • Dinesh Jaishankar
    University of Illinois at Chicago, Chicago, Illinois, United States
  • Deepak Shukla
    University of Illinois at Chicago, Chicago, Illinois, United States
  • Footnotes
    Commercial Relationships   Dinesh Jaishankar, None; Deepak Shukla, None
  • Footnotes
    Support  R01 EY024710
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 4295. doi:
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      Dinesh Jaishankar, Deepak Shukla; A cyclic anti-heparan sulfate peptide provides protection against primary and recurrent herpes simplex virus-1 (HSV-1) infection of the cornea. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4295.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Primary and recurrent ocular herpes infections affect almost 60-90% of the population and in severe cases is one of the leading causes of infectious blindness. This study describes the topical use of a cyclic anti-heparan sulfate peptide that shows promise in blocking ocular herpes infections.

Methods : Cyclic peptide synthesis and confirmation was performed at the Protein Research Laboratory at the University of Illinois at Chicago. A random cyclic peptide sequence was also generated to serve as a control. Cell viability assay via MTT was performed in human corneal epithelial cells (HCE) to rule out non-toxic concentrations. HSV-1 virus entry using a recombinant virus strain encoding the beta-galactosidase gene and viral protein synthesis and replication of HSV-1 were assayed in the presence of the control and treatment cyclic peptides. Using the mouse corneas as a model of ocular infection, the therapeutic activity of the cyclic peptide was examined under primary and recurrent infection conditions (under UV-B exposure) by monitoring the spread of GFP tagged HSV-1 virus in the eye, determining viral shedding from the tears, examining the mice health and clinical symptoms of infection and performing immunohistochemistry for the presence of viral proteins in the eye.

Results : The cyclic peptide showed strong antiviral activity in a non-toxic range. Moreover, it significantly blocked viral entry, viral mRNA and protein production and viral replication and spread. Primary infection in mouse corneas that received the cyclic peptide significantly diminished the progression of HSV-1 infection. A similar effect was seen during the treatment of the reactivated infection.

Conclusions : For the first time, we present the topical application of a cyclic peptide that shows promise in blocking primary as well reactivated HSV-1 infections of the eye. Future studies to test the synergistic effects with an existing topical antiviral: Zirgan (ganciclovir gel) will be tested.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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