title: Generation of neutralizing aptamers against herpes simplex virus type 2: potential components of multivalent microbicides.
abstract: The prophylactic use of topical antiviral agents has recently been validated by the reduction in human immunodeficiency virus (HIV) type 1 infection incidence seen using tonofovir-containing microbicides. In order to develop a wide-spectrum microbicide to prevent infection with a wide range of sexually transmitted viruses, we have previously reported the development of HIV-neutralizing aptamers and here report the isolation and characterization of aptamers that neutralize herpes simplex virus type 2 (HSV-2). These aptamers bind the envelope glycoprotein (gD), are potent (IC(50) of 20-50 nM) and are able to block infection pathways dependent on both major entry receptors, Nectin1 and HVEM. Structural analysis and mutagenesis of these aptamers reveal a core specificity element that could provide the basis for pharmaceutical development. As HSV-2 is a major risk factor for the acquisition of HIV-1, a microbicide capable of preventing HSV-2 infection would not only reduce the morbidity associated with HSV-2, but also that derived from HIV-1.
authors.affiliation: Sir William Dunn School of Pathology, South Parks Road, Oxford OX1 3RE, UK.
authors.forename: M D
authors.initials: MD
authors.lastname: Moore
authors.affiliation: Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: D H J
authors.initials: DHJ
authors.lastname: Bunka
authors.affiliation: Sir William Dunn School of Pathology, South Parks Road, Oxford OX1 3RE, UK.
authors.forename: M
authors.initials: M
authors.lastname: Forzan
authors.affiliation: Magee-Womens Research Institute, 204 Craft Ave, Room B505, Pittsburgh, PA 15213, USA.
authors.forename: P G
authors.initials: PG
authors.lastname: Spear
authors.affiliation: Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: P G
authors.initials: PG
authors.lastname: Stockley
authors.affiliation: Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors.forename: I
authors.initials: I
authors.lastname: McGowan
authors.affiliation: Sir William Dunn School of Pathology, South Parks Road, Oxford OX1 3RE, UK.
authors.forename: W
authors.initials: W
authors.lastname: James
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000494:pharmacology*; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000378:metabolism; D006561:Herpes Simplex / Q000188:drug therapy / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D018258:Herpesvirus 2, Human / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D000075983:Nectins
chemical_list: D000998:Antiviral Agents; D052157:Aptamers, Nucleotide; D015815:Cell Adhesion Molecules; C000619010:NECTIN1 protein, human; D000075983:Nectins