Abstract
Abstract: :
Purpose: Defensins are an important component of the innate immune system that responds immediately to microbial challenge. They are small, positively-charged peptides that are in peripheral white blood cells, produced in ocular tissues, and are present in the tear film. Previous studies demonstrated direct antimicrobial activity of human defensins against a variety of bacteria and enveloped viruses (HSV, CMV, VZV, HIV). Zhang et al (Science, 2002) reported that human alpha defensins are potent inhibitors of HIV isolates and may play an important role in preventing the clinical progression of asymptomatic HIV infection to clinical AIDS in some patients. The goal of the current study was to determine whether human defensins demonstrate direct antiviral inhibitory activity against a non-enveloped virus, adenovirus. Methods: Human alpha defensin-1 (HDEF A1), Human beta defensin-1 (HDEF B1), and Human beta defensin-2 (HDEF B2) were purchased from Peptides International, Louisville, KY. In a direct neutralization-type assay, 100 µg/ml of each defensin or a PBS control were incubated together with stocks of Ad3, Ad5, and Ad19 for 60 minutes at 37oC. After incubation, the mixture of defensin or control and adenovirus was plated on A549 cells and incubated for 7 - 10 days. For each Ad serotype, the percent inhibition was calculated as the residual titers for a given defensin / titer in the mock-treated PBS controls X 100. Results: Conclusions: Human defensins inhibit non-enveloped adenovirus in vitro and may play a role in the rapid innate immune response to adenovirus ocular infection in vivo. Percent Inhibition of Different Ad Serotypes in a Neutralization-type Assay
Keywords: adenovirus • antiviral drugs • immunomodulation/immunoregulation