Human antimicrobial peptides LL-37 and human β-defensin-2 reduce viral replication in keratinocytes infected with varicella zoster virus

Crack, L; Jones, Liza; Malavige, Gathsaurie Neelika; Patel, Vidhi; Ogg, Graham S.

doi:10.1111/j.1365-2230.2012.04305.x

Cited by 57 publications

(46 citation statements)

References 47 publications

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“…The ability of LL-37 to directly inhibit a number of viruses has been reviewed previously (Barlow et al, 2014b), with further activities found against Aichi virus A (Vilas Boas et al, 2017), human adenoviruses 8 and 19 (HAdV-8 and HAdV-19) (Gordon et al, 2005; Uchio et al, 2013), hepatitis C virus (HCV) (Matsumura et al, 2016), human papillomavirus 16 (HPV16) (Buck et al, 2006), human rhinovirus (HRV) (Findlay et al, 2017; Schögler et al, 2016; Sousa et al, 2017), and varicella zoster virus (VZV) (Crack et al, 2012). While LL-37 has only been measured at 0.5 μg/ml in saliva (Bachrach et al, 2006; Takeuchi et al, 2012) and 10 μg/ml in gingival crevicular fluid 29 , the actual physiological concentration may be much higher at sites closer to the oral epithelial cells themselves due to the diffusion of the peptides once released from cells.…”

Section: Discussionmentioning

confidence: 99%

LL-37 disrupts the Kaposi's sarcoma-associated herpesvirus envelope and inhibits infection in oral epithelial cells

2018

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Oral epithelial cells (OECs) represent the first line of defense against viruses that are spread via saliva, including Kaposi's sarcoma-associated herpesvirus (KSHV). Infection of humans by KSHV and viral pathogenesis begins by infecting OECs. One method OECs use to limit viral infections in the oral cavity is the production of antimicrobial peptides (AMPs), or host defense peptides (HDPs). However, no studies have investigated the antiviral activities of any HDP against KSHV. The goal of this study was to determine the antiviral activity of one HDP, LL-37, against KSHV in the context of infecting OECs. Our results show that LL-37 significantly decreased KSHV's ability to infect OECs in both a structure- and dose-dependent manner. However, this activity does not stem from affecting OECs, but instead the virions themselves. We found that LL-37 exerts its antiviral activity against KSHV by disrupting the viral envelope, which can inhibit viral entry into OECs. Our data suggest that LL-37 exhibits a marked antiviral activity against KSHV during infection of oral epithelial cells, which can play an important role in host defense against oral KSHV infection. Thus, we propose that inducing LL-37 expression endogenously in oral epithelial cells, or potentially introducing as a therapy, may help restrict oral KSHV infection and ultimately KSHV-associated diseases.

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Section: Discussionmentioning

confidence: 99%

LL-37 disrupts the Kaposi's sarcoma-associated herpesvirus envelope and inhibits infection in oral epithelial cells

2018

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“…Therefore, we decided to analyse the influence of PRGF on the expression of hBD‐2 in keratinocytes. Human beta‐defensin‐2 is an AMP produced by a number of epithelial cells exhibiting potent antimicrobial activity against bacteria, yeast and viruses . hBD‐2 belongs to the innate epithelial defense system and its expression is induced following stimulation of epithelial cells with micro‐organisms .…”

Section: Discussionmentioning

confidence: 99%

Platelet‐released growth factors induce the antimicrobial peptide human beta‐defensin‐2 in primary keratinocytes

Bayer

Lammel

Rademacher

et al. 2016

Experimental Dermatology

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Platelet-released growth factors (PRGF) and its related clinically used formulations [e.g. Vivostat platelet-rich fibrin (PRF(®) )] are thrombocyte concentrate lysates that support healing of chronic, hard-to-heal and infected wounds. Human beta-defensin-2 (hBD-2) is an antimicrobial peptide expressed in human keratinocytes exhibiting potent antimicrobial activity against wound-related bacteria. In this study, we analysed the influence of PRGF on hBD-2 expression in human primary keratinocytes and the influence of Vivostat PRF(®) on hBD-2 expression in experimentally generated skin wounds in vivo. Treatment of primary keratinocytes with PRGF caused a significant increase in hBD-2 gene and protein expressions in a concentration- and time-dependent manner. The use of blocking antibodies revealed that the PRGF-mediated hBD-2 induction was partially mediated by the epidermal growth factor receptor and the interleukin-6 receptor (IL-6R). Luciferase gene reporter assays indicated that the hBD-2 induction through PRGF required activation of the transcription factor activator protein 1 (AP-1), but not of NF-kappaB. In concordance with these cell culture data, Vivostat PRF(®) induced hBD-2 expression when applied to experimentally generated skin wounds. Together, our results indicate that the induction of hBD-2 by thrombocyte concentrate lysates can contribute to the observed beneficial effects in the treatment of chronic and infected wounds.

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“…This effect could be neutralized by polyanions such as heparin, dextran sulfate, oversulfated heparin, or oversulfated chondroitin sulfate by blocking the binding of SEVI to the virions [63]. Moreover, various cationic defensin peptides have shown antiviral activity [64,65]. In contrast to defensins and antimicrobial peptides, IL-26 did not show antibacterial activity (data not shown).…”

Section: Discussionmentioning

confidence: 99%

The Cationic Cytokine IL-26 Differentially Modulates Virus Infection in Culture

2013

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Interleukin-26 (IL-26) belongs to the IL-10 cytokine family, is produced by activated T cells, and targets epithelial target cells for signal transduction. Here, we describe the IL-26 effects on the infection of culture cells with recombinant vesicular stomatitis virus (VSV), human cytomegalovirus (HCMV), and herpes simplex virus type 1 (HSV-1) expressing green fluorescent protein. After pre-incubation with recombinant IL-26 and at low multiplicity of infection, VSV showed strongly enhanced infection and replication rates as measured for infectivity, for transcript levels, and for protein expression. Control proteins did not affect VSV infection. The IL-26 effect was independent of the IL-26 receptor and neutralized by anti-IL-26 serum. Pre-incubation of VSV was much more efficient than pre-incubation of the target cells to enhance virus infection. IL-26 increased virus adsorption to target cells as shown by quantitative reverse-transcription PCR. In contrast, the infection of IL-26-treated human fibroblasts with HCMV was inhibited and the infection by HSV-1 was not altered by IL-26. Thus, IL-26 differentially modulates the infection by different enveloped viruses.

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Human antimicrobial peptides LL-37 and human β-defensin-2 reduce viral replication in keratinocytes infected with varicella zoster virus

Cited by 57 publications

References 47 publications

LL-37 disrupts the Kaposi's sarcoma-associated herpesvirus envelope and inhibits infection in oral epithelial cells

LL-37 disrupts the Kaposi's sarcoma-associated herpesvirus envelope and inhibits infection in oral epithelial cells

Platelet‐released growth factors induce the antimicrobial peptide human beta‐defensin‐2 in primary keratinocytes

The Cationic Cytokine IL-26 Differentially Modulates Virus Infection in Culture

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