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.

Structural diversity and species distribution of host-defense peptides in frog skin secretions

“…Several frog skin peptides that were first identified on the basis of their ability to inhibit the growth of bacteria have subsequently been shown to inactivate viruses. These include brevinin-1, effective in inactivating herpes simplex virus type 1 and type 2 [89], and caerin 1.1, caerin 1.9, and maculatin 1.1 that completely inhibit HIV infection of T cells within minutes of exposure to virus at concentrations that were not toxic to target cells [90]. Esculentin-2P and ranatuerin-2P, from L. pipiens, dermaseptin-B1 from P. bicolor, and temporin A rapidly inactivated frog virus 3, a potentially pathogenic iridovirus infecting anurans [91,92].…”

Temporins, anti-infective peptides with expanding properties

“…1). In addition to their large spectrum of antibacterial and antifungal activities, several amphibian AMPs can inhibit cell-mediated HIV capture and infection [33]. This review focuses on temporins, a large family of AMPs isolated from frog skin, some of which possess attractive and unique properties that make them good candidates to increase our knowledge about peptide-mediated innate immunity, and promising templates for the future design of new anti-infective agents.…”

Histatin 5-Derived Peptide with Improved Fungicidal Properties Enhances Human Immunodeficiency Virus Type 1 Replication by Promoting Viral Entry

“…One of the complicating factors for the virus is antimicrobial peptides that are secreted at mucosal surfaces as part of the innate immune system. Their use as candidate forms of prophylaxis against HIV-1 has therefore been proposed (5,36,38). There are several studies on antimicrobial peptides and inhibition of HIV-1 replication, and their mode of action is diverse, including disruption of the viral membrane, inhibition of reverse transcription, or prevention of viral entry (5,18,23,32,33,39,43).…”