Antiviral Mechanisms of Human Defensins

Wilson, Sarah S.; Wiens, Mayim E.; Smith, Jason G.

Defensins are an effector component of the innate immune system with broad antimicrobial activity. Humans express two types of defensins, α- and β-defensins, which have antiviral activity against both enveloped and non-enveloped viruses. The diversity of defensin-sensitive viral species reflects a multitude of antiviral mechanisms. These include direct defensin targeting of viral envelopes, glycoproteins, and capsids in addition to inhibition of viral fusion and post-entry neutralization. Binding and modulation of host cell surface receptors and disruption of intracellular signaling by defensins can also inhibit viral replication. In addition, defensins can function as chemokines to augment and alter adaptive immune responses, revealing an indirect antiviral mechanism. Nonetheless, many questions regarding the antiviral activities of defensins remain. Although significant mechanistic data is known for α-defensins, molecular details for β-defensin inhibition are mostly lacking. Importantly, the role of defensin antiviral activity in vivo has not been addressed due to the lack of a complete defensin knockout model. Overall, the antiviral activity of defensins is well established as are the variety of mechanisms by which defensins achieve this inhibition; however, additional research is needed to fully understand the role of defensins in viral pathogenesis.