The Human Cathelicidin LL-37, a Defensive Peptide Against Rotavirus Infection
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LL-37 is a 37 amino acid long cationic peptide belonging to the cathelicidin family of antimicrobial peptides. Limited investigations have shown the antimicrobial potency of LL-37 against different viral infections. We aimed to investigate the effect of the human cathelicidin peptide LL-37 on rotavirus infection, as a causative agent of severe gastroenteritis in children. After evaluation of LL-37 toxicity using methyl thiazolyl tetrazolium and neutral red uptake assays on the MA-104 cells, antiviral activity was assessed both by tissue culture infectious dose 50 (TCID50) and quantitative Real-Time PCR assays. Indirect immunofluorescence assay (IFA) and hematoxylin and eosin (H&E) staining were also performed to further confirm the inhibitory effects of the LL-37 on rotavirus. The viability maintained more than 90% up to the concentration of 50 μg/mL of peptide. LL-37 exerted its antiviral effect only when cells were pre-treated with peptide prior to rotavirus infection. 50 μg/mL of LL-37 could result in 3.36 log10 TCID50 reduction in virus titer (p = 0.0001), and an inhibition rate of 82.2% in copy number of rotavirus genomic RNA was obtained. IFA showed that the expression of rotavirus antigens in cells pre-treated with 50 μg/mL LL-37 is noticeably lower than the virus control. H&E assay also showed that the size and formation of inclusion bodies are decreased in rotavirus-infected cells pre-treated with 50 μg/mL LL-37 as compared to the virus control. Our findings suggested that the LL-37 peptide may interfere with viral attachment or act as an immune regulator, promoting innate immune responses.
KeywordsCathelicidin LL-37 Antiviral activity Rotavirus Antimicrobial peptides Innate immunity In vitro
This work was financially supported by Ferdowsi University of Mashhad, Iran (Grant No. 39199).
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Conflict of interest
The authors declare that they have no conflict of interest.
Research Involving Human and Animal Rights
This article does not contain any studies with human participants or animals performed by any of the authors.
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