title: A 3-O-sulfated heparan sulfate binding peptide preferentially targets herpes simplex virus 2-infected cells.
abstract: Herpes simplex virus 2 (HSV-2) is the primary cause of genital herpes, which is one of the most common sexually transmitted viral infections worldwide and a major cofactor for human immunodeficiency virus infection. The lack of an effective vaccine or treatment and the emergence of drug-resistant strains highlight the need for developing new antivirals for HSV-2. Here, we demonstrate that a low-molecular-weight peptide isolated against 3-O-sulfated heparan sulfate (3-OS HS) can efficiently block HSV-2 infection. Treatment with the peptide inhibited viral entry and cell-to-cell spread both in vitro and in vivo using a mouse model of genital HSV-2 infection. Quite interestingly, the peptide showed a preferential binding to HSV-2-infected cells, with more than 200% increased binding compared to uninfected cells. Our additional results show that heparan sulfate expression is upregulated by 25% upon HSV-2 infection, which is a significant new finding that could be exploited for designing new diagnostic tests and treatment strategies against HSV-2-infected cells. In addition, our results also raise the possibility that 3-OS HS modifications within HS may be upregulated even more to accommodate for a significantly higher increase in the peptide binding to the infected cells.
authors.affiliation: Department of Ophthalmology and Visual Sciences, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Ali
authors.forename: Ghadah A
authors.initials: GA
authors.lastname: Karasneh
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Jarding
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Tiwari
authors.forename: Deepak
authors.initials: D
authors.lastname: Shukla
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D005260:Female; D006497:Heparan Sulfate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006558:Herpes Genitalis / Q000188:drug therapy / Q000378:metabolism / Q000821:virology*; D018258:Herpesvirus 2, Human / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000494:pharmacology*; D011991:Receptors, Virus / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053586:Virus Internalization / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D006497:Heparan Sulfate; D010455:Peptides; D011991:Receptors, Virus