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Antimicrobial Peptides from Amphibian Skin Potently Inhibit Human Immunodeficiency Virus Infection and Transfer of Virus from Dendritic Cells to T Cells

Department of Microbiology and Immunology,¹ Department of Pediatrics,² Department of Medicine,³ Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, Nashville, Tennessee 37232,⁴ AdvancMed, LLC, Lexington, Kentucky 40513,⁵ Department of Chemistry, The University of Adelaide, Australia,⁶ Department of Environmental Biology, The University of Adelaide, Australia,⁷ Department of Biochemistry, United Arab Emirates University, United Arab Emirates,⁸ Wade Research Foundation, Somerset, New Jersey 08873,⁹ HIV Drug Resistance Program, NCI, Frederick, Maryland 21702,¹⁰

Received 3 April 2005/ Accepted 17 June 2005

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.

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