Evaluation of a Panel of Recombinant Respiratory Syncytial Virus (RSV) Strains to Antimicrobial Peptide Inactivation

Indianapolis, IN

Antimicrobial peptides are small proteins that play a critical role in the innate immune response. Previous studies have established an important role of antimicrobial peptides in providing defense and limiting growth of bacterial, fungal, and viral pathogens in the respiratory tract. Respiratory syncytial virus (RSV) is an upper and lower respiratory pathogen which is associated with severe disease in young infants and the elderly. Efforts to develop a vaccine for RSV have been hindered by physical and genetic instabilities, poor immunogenicity, and a legacy of vaccine-enhanced disease. Therapeutic options after onset of symptoms are limited for RSV and the host events associated with RSV clearance remain unclear. Recently, several studies have shown that a class of antimicrobial peptides called defensins and a separate antimicrobial peptide, cathelicidin (LL-37), were able to inactivate the RSV laboratory strain A2. However, these studies were limited to this laboratory strain and appreciable differences in the structure and replication among RSV strains are known to exist. In this study, we evaluated the efficacy of human defensins and LL-37 on inactivation of a panel of recombinant RSV strains that express the attachment and fusion proteins of laboratory and clinical strains of RSV. We used a combination of inactivation assays and replication assays to more clearly define the susceptibility of RSV strains to antimicrobial peptide inactivation. These studies illustrate a clear role of antimicrobial peptides in limiting RSV infection and may provide new therapeutic targets to treat active RSV infections.