Anti-HIV-1 activity of indolicidin, an antimicrobial peptide from neutrophils

• DOI: 10.1002/jlb.63.1.94
• Publication Date: 2018-01-12T19:03:42Z
• Authors: W Edward Robinson; Brenda McDougall; Dat Tran; Michael E Selsted
• Keywords: CD4-Positive T-Lymphocytes; 0301 basic medicine; Anti-HIV Agents; Cell Survival; Neutrophils; Temperature; HIV Infections; 3. Good health; Structure-Activity Relationship; 03 medical and health sciences; Animals; Humans; Cattle; Peptides; Cells, Cultured; Antimicrobial Cationic Peptides

Abstract Indolicidin is a tridecapeptide amide isolated from the cytoplasmic granules of bovine neutrophils. It has potent, broad spectrum microbicidal activities in vitro that are thought to be related to the membrane-disruptive properties of the peptide. Based on the putative membrane-targeted mode of action, we postulated that indolicidin would be active against HIV-1, an enveloped virus. Indolicidin was reproducibly virucidal against HIV-1 at a concentration of 333 μg/mL (174 μM) with a 50% inhibitory dose between 67 and 100 μg/mL. At 37°, killing was rapid with >50% killing of HIV occurring within 5 min, and nearly 100% viral inactivation achieved by 60 min. The anti-HIV activity of indolicidin was temperature-sensitive, a finding consistent with a membrane-mediated antiviral mechanism. Parallel experiments revealed that indolicidin lysed cultured lymphoblastoid cells at concentrations similar to those required for antiviral activity. However, a des-R13-amide indolicidin analog (R12-OH), previously shown to have less antibacterial activity than indolicidin, was significantly less active against HIV and was non-toxic to lymphoid target cells at concentrations up to 333 μg/mL, the highest level tested.