title: Anti-HSV activity of serpin antithrombin III.
abstract: Natural serine protease inhibitors (serpins) elicit sensing of a microbial cell intruder and activate an intrinsic cellular immune response in HIV and HCV infected cells. Here, we demonstratein vitroinhibition of HSV with serpin antithrombin III (ATIII) early during infection pointing towards inhibition of an entry event. We also found reduction of mortality from 90% to 40% in an abrasion mice model demonstrating a strong reduction of infectionin vivo. Our data also indicated that this treatment might be suitable for drug-resistant viruses since high inhibition of an acyclovir-resistant HSV-1 strain was found. Thus, an ATIII tropical treatment might be used for immunocompromised patients where prolonged treatment leads to drug resistant HSV-1 strains. Understanding how ATIII regulates HSV-1 infections may reveal new avenues for therapeutic interventions.
authors.affiliation: Department of Pediatrics, University of Alabama at Birmingham, USA.
authors.forename: Debra C
authors.initials: DC
authors.lastname: Quenelle
authors.affiliation: Imquest BioSciences, Inc., Frederick, Maryland, USA.
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Hartman
authors.affiliation: Imquest BioSciences, Inc., Frederick, Maryland, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Buckheit
authors.affiliation: Department of Pediatrics, University of Alabama at Birmingham, USA.
authors.forename: Mark N
authors.initials: MN
authors.lastname: Prichard
authors.affiliation: Acceleration BioPharmaceuticals, Inc. Woburn, MA, USA.
authors.forename: Ralf Geiben
authors.initials: RG
authors.lastname: Lynn
keywords: Antithrombin III; HSV; acyclovir-resistant HSV-1; mice abrasion model; serine protease inhibitor; serpin