title: Prophylactic, therapeutic and neutralizing effects of zinc oxide tetrapod structures against herpes simplex virus type-2 infection.
abstract: The attachment of Herpes simplex virus type-2 (HSV-2) to a target cell requires ionic interactions between negatively charged cell surface co-receptor heparan sulfate (HS) and positively charged residues on viral envelop glycoproteins, gB and gC. Effective blocking of this first step of HSV-2 pathogenesis demonstrates significant prophylactic effects against the viral disease; any in vitro therapeutic effects of blocking this interaction, however, are not clear. Here, we provide new evidence that zinc oxide tetrapod micro-nanostructures synthesized by flame transport approach significantly block HSV-2 entry into target cells and, in addition, demonstrate the potential to stop the spread of the virus among already infected cells. The zinc oxide tetrapods (ZnOTs) also exhibit the ability to neutralize HSV-2 virions. Natural target cells such as human vaginal epithelial and HeLa cells showed highly reduced infectivity when infected with HSV-2 virions that were pre-incubated with the ZnOTs. The mechanism behind the ability of ZnOTs to prevent, neutralize or reduce HSV-2 infection relies on their ability to bind the HSV-2 virions. We used fluorescently labeled ZnOTs and GFP-expressing HSV-2 virions to demonstrate the binding of the ZnOTs with HSV-2. We also show that the binding and hence, the antiviral effects of ZnOTs can be enhanced by illuminating the ZnOTs with UV light. Our results provide new insights into the anti-HSV-2 effects of ZnOT and rationalize their development as a HSV-2 trapping agent for the prevention and/or treatment of infection. The observed results also demonstrate that blocking HSV-2 attachment can have prophylactic as well as therapeutic applications.
authors.affiliation: Department of Ophthalmology & Visual Sciences, University of Illinois at Chicago, IL 60612, USA.
authors.forename: Thessicar E
authors.initials: TE
authors.lastname: Antoine
authors.forename: Yogendra K
authors.initials: YK
authors.lastname: Mishra
authors.forename: James
authors.initials: J
authors.lastname: Trigilio
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Tiwari
authors.forename: Rainer
authors.initials: R
authors.lastname: Adelung
authors.forename: Deepak
authors.initials: D
authors.lastname: Shukla
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D016466:CHO Cells; D002470:Cell Survival; D006224:Cricetinae; D004847:Epithelial Cells / Q000166:cytology / Q000821:virology; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006561:Herpes Simplex / Q000188:drug therapy* / Q000517:prevention & control; D018258:Herpesvirus 2, Human / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D049329:Nanostructures; D009500:Neutralization Tests; D014621:Vagina / Q000166:cytology; D010948:Viral Plaque Assay; D053585:Virus Attachment; D053586:Virus Internalization / Q000187:drug effects*; D015034:Zinc Oxide / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D049452:Green Fluorescent Proteins; D015034:Zinc Oxide