title: Inhibition of HIV infection by caerin 1 antimicrobial peptides.
abstract: The major mode of transmission of the human immunodeficiency virus (HIV) is by sexual intercourse. In the effort to halt the spread of HIV, one measure that holds great promise is the development of effective microbicides that can prevent transmission. Previously we showed that several amphibian antimicrobial peptides (AMPs) completely inhibit HIV infection of T cells while maintaining good viability of the T cell targets. These peptides also inhibited the transfer of HIV by dendritic cells (DCs) to T cells when added up to 8h after virus exposure. Here we report on the anti-HIV activity of 18 additional structurally related caerin 1 family peptides in comparison with our previous best candidate caerin 1.9. Nine peptides were equally effective or more effective in the inhibition of T cell infection and disruption of the HIV envelope as caerin 1.9. Of those nine peptides, three peptides (caerin 1.2, caerin 1.10, and caerin 1.20) exhibited excellent inhibition of HIV infectivity at low concentrations (12-25μM) and limited toxicity against target T cells and endocervical epithelial cells. There was a direct correlation between the effectiveness of the peptides in disruption of the viral envelope and their capacity to inhibit infection. Thus, several additional caerin 1 family peptides inhibit HIV infection have limited toxicity for vaginal epithelial cells, and would be good candidates for inclusion in microbicide formulations.
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, United States.
authors.forename: Scott
authors.initials: S
authors.lastname: VanCompernolle
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, United States.
authors.forename: Patricia B
authors.initials: PB
authors.lastname: Smith
authors.affiliation: Department of Chemistry, The University of Adelaide, Australia.
authors.forename: John H
authors.initials: JH
authors.lastname: Bowie
authors.affiliation: Department of Environmental Biology, The University of Adelaide, Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Tyler
authors.affiliation: Department of Microbiology, The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, United States.
authors.forename: Derya
authors.initials: D
authors.lastname: Unutmaz
authors.affiliation: Departments of Pathology, Microbiology and Immunology, and of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232, United States; Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, United States. Electronic address: louise.rollins-smith@vanderbilt.edu.
authors.forename: Louise A
authors.initials: LA
authors.lastname: Rollins-Smith
mesh_terms: D029845:Amphibian Proteins / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology*
chemical_list: D029845:Amphibian Proteins; D023181:Antimicrobial Cationic Peptides
keywords: Antimicrobial peptides; Caerin 1; Endocervical epithelial cells; Human immunodeficiency virus; Lymphocytes