Peptides against influenza: evaluating the anti-viral characteristics of regenerating Islet Derived Protein 3 and the cathelicidin LL-37
Antimicrobial peptides (AMPs) are innate host defense peptides that protect against pathogenic microbes by neutralizing toxins or via a direct killing mechanism. AMPs are classified based on their physical properties such as charge, structure, and binding motifs. Here we investigated the antimicr...
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ndltd-bu.edu-oai-open.bu.edu-2144-420582021-02-20T05:01:16Z Peptides against influenza: evaluating the anti-viral characteristics of regenerating Islet Derived Protein 3 and the cathelicidin LL-37 De Luna, Xavier Castillo Hartshorn, Kevan L. Immunology Antimicrobial peptides Influenza Innate Immunity Antimicrobial peptides (AMPs) are innate host defense peptides that protect against pathogenic microbes by neutralizing toxins or via a direct killing mechanism. AMPs are classified based on their physical properties such as charge, structure, and binding motifs. Here we investigated the antimicrobial and immune-modulating effects of the Regenerating Islet-Derived Protein 3 (REG3) family and LL-37 REG3 peptides are C-type lectins and have been demonstrated to have antimicrobial activity against Gram-positive bacteria by binding to sugars on the peptidoglycan membrane of these bacteria. A similar strategy is also employed by the lectin Surfactant Protein-D which has been shown to bind and neutralize Influenza A Virus (IAV). REG3 peptides were shown to be expressed in the lungs of mice infected with IAV. We observed reduction of IAV infected cells when IAV was pre-incubated with an Escherichia coliexpressed recombinant version of human REG3A peptide. This peptide also modified interaction of IAV with primary human neutrophils. However, these effects were lost when using a mammalian cell expressed recombinant REG3A. A second member of the REG3 family, REG3G, showed minimal inhibition of IAV infection. While the mechanism remains unclear, LL-37 has demonstrated killing activity against a spectrum of microbes including IAV. Previous work from our group identified the core domain of LL-37 responsible for IAV neutralization. In addition, our group showed that LL-37 modulates interaction of IAV with neutrophils. Here we tested three modified versions of LL-37 that retain the overall size and charge of LL-37, but with modifications in the core domain reducing hydrophobicity. We observed that these mutants retain IAV killing activity across multiple strains. In addition, these mutants retain the modulation of IAV induced neutrophil responses. We also found that the compounds sodium butyrate and Entinostat, which can upregulate endogenous expression of LL-37, have variable effects in IAV infection. We believe these findings will aid in the development of LL-37 derivatives to expand the repertoire of antimicrobials. 2021-02-18T19:01:59Z 2021-02-18T19:01:59Z 2020 2021-02-16T17:04:32Z Thesis/Dissertation https://hdl.handle.net/2144/42058 0000-0002-8266-8594 en_US |
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Immunology Antimicrobial peptides Influenza Innate Immunity |
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Immunology Antimicrobial peptides Influenza Innate Immunity De Luna, Xavier Castillo Peptides against influenza: evaluating the anti-viral characteristics of regenerating Islet Derived Protein 3 and the cathelicidin LL-37 |
description |
Antimicrobial peptides (AMPs) are innate host defense peptides that protect against
pathogenic microbes by neutralizing toxins or via a direct killing mechanism. AMPs are
classified based on their physical properties such as charge, structure, and binding motifs.
Here we investigated the antimicrobial and immune-modulating effects of the
Regenerating Islet-Derived Protein 3 (REG3) family and LL-37
REG3 peptides are C-type lectins and have been demonstrated to have antimicrobial
activity against Gram-positive bacteria by binding to sugars on the peptidoglycan
membrane of these bacteria. A similar strategy is also employed by the lectin Surfactant
Protein-D which has been shown to bind and neutralize Influenza A Virus (IAV). REG3
peptides were shown to be expressed in the lungs of mice infected with IAV. We observed
reduction of IAV infected cells when IAV was pre-incubated with an Escherichia coliexpressed
recombinant version of human REG3A peptide. This peptide also modified
interaction of IAV with primary human neutrophils. However, these effects were lost when
using a mammalian cell expressed recombinant REG3A. A second member of the REG3
family, REG3G, showed minimal inhibition of IAV infection.
While the mechanism remains unclear, LL-37 has demonstrated killing activity against a
spectrum of microbes including IAV. Previous work from our group identified the core
domain of LL-37 responsible for IAV neutralization. In addition, our group showed that
LL-37 modulates interaction of IAV with neutrophils. Here we tested three modified
versions of LL-37 that retain the overall size and charge of LL-37, but with modifications
in the core domain reducing hydrophobicity. We observed that these mutants retain IAV
killing activity across multiple strains. In addition, these mutants retain the modulation of
IAV induced neutrophil responses. We also found that the compounds sodium butyrate and
Entinostat, which can upregulate endogenous expression of LL-37, have variable effects in
IAV infection. We believe these findings will aid in the development of LL-37 derivatives
to expand the repertoire of antimicrobials. |
author2 |
Hartshorn, Kevan L. |
author_facet |
Hartshorn, Kevan L. De Luna, Xavier Castillo |
author |
De Luna, Xavier Castillo |
author_sort |
De Luna, Xavier Castillo |
title |
Peptides against influenza: evaluating the anti-viral characteristics of regenerating Islet Derived Protein 3 and the cathelicidin LL-37 |
title_short |
Peptides against influenza: evaluating the anti-viral characteristics of regenerating Islet Derived Protein 3 and the cathelicidin LL-37 |
title_full |
Peptides against influenza: evaluating the anti-viral characteristics of regenerating Islet Derived Protein 3 and the cathelicidin LL-37 |
title_fullStr |
Peptides against influenza: evaluating the anti-viral characteristics of regenerating Islet Derived Protein 3 and the cathelicidin LL-37 |
title_full_unstemmed |
Peptides against influenza: evaluating the anti-viral characteristics of regenerating Islet Derived Protein 3 and the cathelicidin LL-37 |
title_sort |
peptides against influenza: evaluating the anti-viral characteristics of regenerating islet derived protein 3 and the cathelicidin ll-37 |
publishDate |
2021 |
url |
https://hdl.handle.net/2144/42058 |
work_keys_str_mv |
AT delunaxaviercastillo peptidesagainstinfluenzaevaluatingtheantiviralcharacteristicsofregeneratingisletderivedprotein3andthecathelicidinll37 |
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1719378066173591552 |