α, β, and θ defensins are effectors of the innate immune system with potent antibacterial, antiviral, and antifungal activity. Defensins have direct antiviral activity in cell culture, with varied mechanisms for individual viruses, although some common themes have emerged. In addition, defensins have potent immunomodulatory activity that can alter innate and adaptive immune responses to viral infection. In some cases, there is evidence for paradoxical escape from defensin neutralization or enhancement of viral infection. The direct and indirect activities of defensins have led to their development as therapeutics and vaccine components. The major area of investigation that continues to lag is the connection between the effects of defensins in cell culture models and viral pathogenesis in vivo. Model systems to study defensin biology, including more physiologic models designed to bridge this gap, are also discussed.

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