Antiviral Potential of Cathelicidins

Barlow, Peter G.; Findlay, Emily Gwyer; Currie, S.; Davidson, Donald J.

doi:10.2217/fmb.13.135

Cited by 69 publications

(66 citation statements)

References 199 publications

(265 reference statements)

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“…Two major families have been characterized in humans, defensins and cathelicidins, and peptides from both families have been demonstrated to possess potent immunomodulatory and antimicrobial activities (reviewed in Refs. [5][6][7]. These peptides are regarded as key elements of the innate immune system.…”

mentioning

confidence: 99%

Carbon Nanoparticles Inhibit the Antimicrobial Activities of the Human Cathelicidin LL-37 through Structural Alteration

Findlay

Pohl

Svoboda

et al. 2017

The Journal of Immunology

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Host defense peptides, also known as antimicrobial peptides, are key elements of innate host defense. One host defense peptide with well-characterized antimicrobial activity is the human cathelicidin, LL-37. LL-37 has been shown to be upregulated at sites of infection and inflammation and is regarded as one of the primary innate defense molecules against bacterial and viral infection. Human exposure to combustion-derived or engineered nanoparticles is of increasing concern, and the implications of nanomaterial exposure on the human immune response is poorly understood. However, it is widely acknowledged that nanoparticles can interact strongly with several immune proteins of biological significance, with these interactions resulting in structural and functional changes of the proteins involved. This study investigated whether the potent antibacterial and antiviral functions of LL-37 were inhibited by exposure to, and interaction with, carbon nanoparticles, together with characterizing the nature of the interaction. LL-37 was exposed to carbon black nanoparticles in vitro, and the antibacterial and antiviral functions of the peptide were subsequently assessed. We demonstrate a substantial loss of antimicrobial function when the peptide was exposed to low concentrations of nanomaterials, and we further show that the nanomaterial-peptide interaction resulted in a significant change in the structure of the peptide. The human health implications of these findings are significant, as, to our knowledge, this is the first evidence that nanoparticles can alter host defense peptide structure and function, indicating a new role for nanoparticle exposure in increased disease susceptibility.

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mentioning

confidence: 99%

Carbon Nanoparticles Inhibit the Antimicrobial Activities of the Human Cathelicidin LL-37 through Structural Alteration

Findlay

Pohl

Svoboda

et al. 2017

The Journal of Immunology

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“…The cathelicidins synthesized in the vagina in response to the ssRNA visues may play role to attack those viruses together with proinflammatory cytokines. Although antiviral properties of cathelicidins had received little attention, recent studies suggest they may attack DNA and RNA viruses by causing damage of the viral envelope (Barlow et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…Cathelicidins are one of the members of host defense peptides with antimicrobial and antiviral activities (Barlow et al, 2014). They are widely expressed in the bone marrow, neutrophils and epithelial tissues of animals such as sheep, cattle, goat (Brogden et al, 2001;Whelehan et al, 2014;Zhang et al, 2014) as well as in chicken (Xiao et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Effects of Virus-associated Molecular Patterns on the Expression of Cathelicidins in the Hen Vagina

2016

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The aim of this study was to examine the expression profiles of the cathelicidins (CATHs) in the oviduct and the effects of Toll-like receptor (TLR) ligands of virus-associated molecular patterns on CATHs expression in the vagina of hens. The mRNA expression of cathelicidins (CATH1, -2, -3 and -B1) in the oviductal mucosa was analyzed by RT-PCR. The effects of viral moleculs on the CATHs expression in the vagina was examined by incubating the mucosal tissue with virus molecular patterns, including poly I:C (dsRNA virus, TLR3 ligand), R848 (ssRNA virus, TLR7 ligand) and CpG-ODN (DNA virus, TLR21 ligand), followed by real-time PCR analysis. The expression of CATH1, CATH2 and CATH3 was identified in all oviductal segments, except for CATH2 which was lacked in the magnum. The expression of CATHB1 was not identified at any segments of the oviduct. Poly I:C down-regulated the expression of CATH1, -2 and -3, whereas R848 up-regulated the expression of CATH1 and CATH3 but down-regulated the expression of CATH2. CpG-ODN did not affect the CATHs expression. These results suggest that mucosal tissues of the oviduct express CATHs to provide the defense mechanism against microbes, and the expression of CATH1 and CATH3 is up-regulated against ssRNA viruses, whereas, dsRNA virus may suppress the expression of CATH1, -2 and -3.

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“…Defensins and cathelicidins are antimicrobial polypeptides that can be constitutively produced by the host or induced after innate immune recognition of pathogens 284 . Two excellent recent reviews refer to the BSA activities of these host defense factors 285 286 . Interestingly, defensins seem to be conserved among different organisms.…”

Section: Host Defense Factorsmentioning

confidence: 99%

“…Cathelicidins are another type of defense peptides that carry a conserved cathelin-like domain 288 . Barlow and colleagues have recently reviewed the BSA effect of cathelicidins 285 . In particular, the human cathelicidin LL-37 has been shown to affect several viruses including VV, RSV, influenza virus, HIV, HSV, DENV and AdV by distinct mechanisms such as envelope disruption and polymerase or protease inhibition 285 .…”

Section: Host Defense Factorsmentioning

confidence: 99%

Antiviral drug discovery: broad-spectrum drugs from nature

et al. 2015

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, but cannot be converted to PDF. You must view these files (e.g. movies) online.Scheme 1_(structures 1-5)_named.cdx Scheme 2_(structures 6-8)_named.cdx Scheme 3_(structure 9)_named.cdx Scheme 4_(structure 10)_named.cdx Scheme 5_ (structures 11-12) The development of drugs with broad-spectrum antiviral activities is a long pursued goal in drug discovery. It has been shown that blocking co-opted host-factors abrogates the replication of many viruses, yet the development of such host-targeting drugs has been met with skepticism mainly due to toxicity issues and poor translation to in vivo models. With the advent of new and more powerful screening assays and prediction tools, the idea of a drug that can efficiently treat a wide range of viral infections by blocking specific host functions has rebloomed. Here we critically review the state-of-the-art in broad-spectrum antiviral drug discovery. We discuss putative targets and treatment strategies, taking particular focus on natural products as promising starting points for antiviral lead development.

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Antiviral Potential of Cathelicidins

Cited by 69 publications

References 199 publications

Carbon Nanoparticles Inhibit the Antimicrobial Activities of the Human Cathelicidin LL-37 through Structural Alteration

Carbon Nanoparticles Inhibit the Antimicrobial Activities of the Human Cathelicidin LL-37 through Structural Alteration

Effects of Virus-associated Molecular Patterns on the Expression of Cathelicidins in the Hen Vagina

Antiviral drug discovery: broad-spectrum drugs from nature

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