title: Antimicrobial peptides from amphibian skin potently inhibit human immunodeficiency virus infection and transfer of virus from dendritic cells to T cells.
abstract: Topical antimicrobicides hold great promise in reducing human immunodeficiency virus (HIV) transmission. Amphibian skin provides a rich source of broad-spectrum antimicrobial peptides including some that have antiviral activity. We tested 14 peptides derived from diverse amphibian species for the capacity to inhibit HIV infection. Three peptides (caerin 1.1, caerin 1.9, and maculatin 1.1) completely inhibited HIV infection of T cells within minutes of exposure to virus at concentrations that were not toxic to target cells. These peptides also suppressed infection by murine leukemia virus but not by reovirus, a structurally unrelated nonenveloped virus. Preincubation with peptides prevented viral fusion to target cells and disrupted the HIV envelope. Remarkably, these amphibian peptides also were highly effective in inhibiting the transfer of HIV by dendritic cells (DCs) to T cells, even when DCs were transiently exposed to peptides 8 h after virus capture. These data suggest that amphibian-derived peptides can access DC-sequestered HIV and destroy the virus before it can be transferred to T cells. Thus, amphibian-derived antimicrobial peptides show promise as topical inhibitors of mucosal HIV transmission and provide novel tools to understand the complex biology of HIV capture by DCs.
authors.affiliation: Department of Microbiology and Immunology, Vanderbilt University School of Medicine, 21st Ave. South, Medical Center North, Room AA5206, Nashville, TN 37232-2363, USA.
authors.forename: Scott E
authors.initials: SE
authors.lastname: VanCompernolle
authors.forename: R Jeffery
authors.initials: RJ
authors.lastname: Taylor
authors.forename: Kyra
authors.initials: K
authors.lastname: Oswald-Richter
authors.forename: Jiyang
authors.initials: J
authors.lastname: Jiang
authors.forename: Bryan E
authors.initials: BE
authors.lastname: Youree
authors.forename: John H
authors.initials: JH
authors.lastname: Bowie
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Tyler
authors.forename: J Michael
authors.initials: JM
authors.lastname: Conlon
authors.forename: David
authors.initials: D
authors.lastname: Wade
authors.forename: Christopher
authors.initials: C
authors.lastname: Aiken
authors.forename: Terence S
authors.initials: TS
authors.lastname: Dermody
authors.forename: Vineet N
authors.initials: VN
authors.lastname: KewalRamani
authors.forename: Louise A
authors.initials: LA
authors.lastname: Rollins-Smith
authors.forename: Derya
authors.initials: D
authors.lastname: Unutmaz
mesh_terms: D000595:Amino Acid Sequence; D000663:Amphibians / Q000235:genetics / Q000276:immunology; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000494:pharmacology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000821:virology*; D006678:HIV / Q000187:drug effects*; D015658:HIV Infections / Q000517:prevention & control* / Q000635:transmission; D006801:Humans; D007113:Immunity, Innate; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D012867:Skin / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000821:virology*
chemical_list: D023181:Antimicrobial Cationic Peptides