Human antimicrobial peptides LL-37 and human β-defensin-2 reduce viral replication in keratinocytes infected with varicella zoster virus.
BACKGROUND
There is mounting evidence that antimicrobial peptides have an important role in cutaneous defence, but the expression of these antimicrobial peptides in atopic eczema (AE) is still unclear. There are several families of antimicrobial peptides, including cathelicidins and human β-defensins. Patients with AE are more susceptible to severe cutaneous viral infections, including varicella zoster virus (VZV).


OBJECTIVE
To characterize the functional activity of the antimicrobial peptides LL-37 (human cathelicidin) and human β-defensin (hBD)-2 keratinocytes were infected with VZV, in a skin-infection model.


METHODS
Flow-cytometry analysis was used to investigate LL-37 expression in normal human keratinocytes, and quantitative PCR was used to determine viral loads in infected HaCaT keratinocytes and B cells, with and without exogenous LL-37 and hBD-2.


RESULTS
LL-37 expression was present in keratinocytes, and both exogenous LL-37 and hBD-2 significantly reduced VZV load in infected keratinocytes and B cells. Specific antibodies blocked the antiviral action exhibited by these antimicrobial peptides. Pre-incubation of VZV with LL-37, but not hBD-2, further reduced VZV load.


CONCLUSIONS
Both LL-37 and hBD-2 have an antiviral effect on VZV replication in the keratinocyte HaCaT cell line and in B cells, but their mechanism of action is different. Evidence of the relationship between antimicrobial peptide expression and higher susceptibility to infections in AE skin is still emerging. Developing novel antiviral therapies based on antimicrobial peptides may provide improved treatment options for patients with AE.
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford and NIHR Research Centre, Oxford, Oxfordshire, UK.
L R
LR
Crack
L
L
Jones
G N
GN
Malavige
V
V
Patel
G S
GS
Ogg
D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology; D001402:B-Lymphocytes / Q000821:virology; D016923:Cell Death / Q000502:physiology; D002478:Cells, Cultured; D005434:Flow Cytometry; D006562:Herpes Zoster / Q000378:metabolism / Q000821:virology; D014645:Herpesvirus 3, Human; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism* / Q000821:virology*; D016133:Polymerase Chain Reaction; D019562:Viral Load; D014779:Virus Replication / Q000502:physiology; D023083:beta-Defensins / Q000494:pharmacology / Q000502:physiology*; D054804:Cathelicidins
D023181:Antimicrobial Cationic Peptides; C106641:DEFB4A protein, human; D023083:beta-Defensins; D054804:Cathelicidins