Cathelicidin antimicrobial peptides suppress EV71 infection via regulating antiviral response and inhibiting viral binding.
Yu. Jie J; Dai. Yue Y; Fu. Yuxuan Y; Wang. Kezhen K; Yang. Yang Y; Li. Min M; Xu. Wei W; Wei. Lin L
Key Findings
- CRAMP levels rise in mice after EV71 infection and this coincides with reduced viral replication
- LL‑37 and CRAMP lower cell damage, viral RNA, VP1 protein, and released virus in human U251 cells
- These peptides increase baseline interferon‑β and IRF3 activation, modestly boost the response to infection, and cut IL‑6 and p38 MAPK signaling
- LL‑37 and CRAMP directly block EV71 from binding to host cells
Practical Outcomes
- For biohackers, LL‑37 appears promising as an immune‑modulating antiviral peptide, but it’s still early‑stage research. No human dosage or safety data exist yet, so any use would be experimental. If you’re interested in antiviral support, keep an eye on future studies and consider that LL‑37 may eventually be formulated as a supplement or topical agent after proper testing.
Summary
The study shows that the human peptide LL‑37 (and its mouse version CRAMP) can curb infection by Enterovirus 71, a common non‑enveloped virus, by boosting the cell’s antiviral defenses and stopping the virus from attaching to cells. It isn’t directly killing the virus but helps the immune response and reduces inflammation. While the work is done in mouse tissue and cultured brain cells, it suggests LL‑37 might be a useful antiviral tool, though real‑world dosing and safety are still unknown.
Abstract
Cathelicidin antimicrobial peptides (human LL-37 and mouse CRAMP) are mainly virucidal to enveloped virus. However, the effects and relative mechanisms of LL-37 and CRAMP on non-enveloped virus are elusive. We herein found that CRAMP expression was significantly up-regulated post non-enveloped Enterovirus 71 (EV71) infection in different tissues of newborn ICR mice, while EV71 replication gradually declined post CRAMP up-regulation, indicating the antiviral potential of cathelicidin against EV71. In vitro antiviral assay showed that LL-37 and CRAMP markedly reduced cytopathic effects (CPE), intracellular viral RNA copy numbers, viral VP1 protein levels, and extracellular virons in U251 cells post EV71 infection, indicating that LL-37 and CRAMP significantly inhibited EV71 replication. Mechanism of action assay showed that LL-37 and CRAMP were not virucidal to EV71, but markedly regulated antiviral immune response in U251 cells. Co-incubation of LL-37 or CRAMP with U251 cells markedly increased the basal interferon-β (IFN-β) expression and interferon regulatory transcription factor 3 (IRF3) phosphorylation, modestly enhanced IFN-β production and IRF3 phosphorylation upon EV71 infection, and significantly reduced interleukin-6 (IL-6) production and p38 mitogen-activated protein kinase (MAPK) activation post EV71 infection. Additionally, LL-37 and CRAMP directly inhibited viral binding to U251 cells. Collectively, LL-37 and CRAMP markedly inhibited EV71 replication via regulating antiviral response and inhibiting viral binding, providing potent candidates for peptide drug development against EV71 infection.
Study Information
pubmed
2021
2021-01-26T00:00:00.000Z
10.1016/j.antiviral.2021.105021
40
58