Antiviral mechanisms of human defensins

Abstract

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 are 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.

Keywords: BK virus; BKV; CMV; DC; HAdV; HBD; HD; HIV; HNP; HPIV; HPV; HRV; HSV; IAV; LTB4; MBD; PBMC; PIV; PKC; RSV; SBD1; VSV; antimicrobial peptides; cytomegalovirus; defensin; dendritic cell; herpes simplex virus; human adenovirus; human defensin; human immunodeficiency virus; human neutrophil peptide; human papillomavirus; human parainfluenza virus; human rhinovirus; human β-defensin; influenza A virus; innate immunity; leukotriene B4; murine β-defensin; parainfluenza virus; peripheral blood mononuclear cell; protein kinase C; respiratory syncytial virus; sheep β-defensin 1; vesicular stomatitis virus; virus.

Graphical abstract

Fig. 1

Major antiviral mechanisms of defensins. Defensins inhibit many steps in enveloped and non-enveloped viral infections. Mechanistic information is available for RSV, HPIV, HIV, HSV, IAV, BKV, HAdV, and HPV. Most mechanisms impact viral entry, but post-entry effects have been described. We have omitted defensin effects that have been reported, but their contribution to blocking infection is in doubt (e.g., aggregation of HAdV by α-defensins). Note that although the defensins relevant for each virus at each step are indicated in broad classifications (e.g., β-defensins), in most cases, not all of the defensins within these groups have been tested or have equivalent activity.