Cathelicidins display conserved direct antiviral activity towards rhinovirus

Sousa, Filipa Henderson; Casanova, Víctor; Findlay, Fern; Stevens, Craig; Svoboda, Pavel; Pohl, Jan; Proudfoot, Lorna; Barlow, Peter G.

doi:10.1016/j.peptides.2017.07.013

Cited by 75 publications

(74 citation statements)

References 52 publications

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“…The activity of the native LL-37 was significantly greater than scrLL-37, leading us to conclude that LL-37 had a structure-dependent antiviral activity against KSHV. This ability of the native primary structure of LL-37 to inhibit viral infections as opposed to a scrambled version of the peptide has also been observed with a number of other viruses—including DENV (Alagarasu et al, 2017), HAdV19 (Gordon et al, 2005), HCV (Matsumura et al, 2016), HRV (Sousa et al, 2017), HSV-1 (Gordon et al, 2005; Lee et al, 2014), influenza A virus (Barlow et al, 2011; Tripathi et al, 2015a, 2013 White et al, 2017), and RSV (Currie et al, 2013; Harcourt et al, 2016)—suggesting the specific structure, and not simply the charge, of LL-37 is important in its antiviral activity.…”

Section: Discussionmentioning

confidence: 61%

“…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%

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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: 61%

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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“…However, the potent antibacterial activity of LL-37 was lost following the addition of carbon black nanoparticles. We recently demonstrated a significant role for cathelicidins in the innate response to influenza virus (45) and rhinovirus 1B (46), and these data suggest that the antiviral activity of LL-37 was also reduced by exposure to nanomaterials. FIGURE 6.…”

Section: Discussionmentioning

confidence: 95%

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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“…The modulation of viral components necessary for replication and infection (such as HIV reverse transcriptase) has also been described [44]. Moreover, LL-37 showed antiviral activity against non-enveloped virus such as adenovirus, Aichi virus, and rhinovirus [100,115,116]. However, it is suggested that this peptide uses a different mechanism to inhibit non-enveloped viruses such as the adenovirus strains.…”

Section: Avps Derived From Mammalsmentioning

confidence: 99%

Antiviral peptides as promising therapeutic drugs

Boas

Campos

Berlanda

et al. 2019

Cell. Mol. Life Sci.

229

175

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While scientific advances have led to large-scale production and widespread distribution of vaccines and antiviral drugs, viruses still remain a major cause of human diseases today. The ever-increasing reports of viral resistance and the emergence and re-emergence of viral epidemics pressure the health and scientific community to constantly find novel molecules with antiviral potential. This search involves numerous different approaches, and the use of antimicrobial peptides has presented itself as an interesting alternative. Even though the number of antimicrobial peptides with antiviral activity is still low, they already show immense potential to become pharmaceutically available antiviral drugs. Such peptides can originate from natural sources, such as those isolated from mammals and from animal venoms, or from artificial sources, when bioinformatics tools are used. This review aims to shed some light on antimicrobial peptides with antiviral activities against human viruses and update the data about the already well-known peptides that are still undergoing studies, emphasizing the most promising ones that may become medicines for clinical use.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Cathelicidins display conserved direct antiviral activity towards rhinovirus

Cited by 75 publications

References 52 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

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

Antiviral peptides as promising therapeutic drugs

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