On Jan, 2021, researchers at Dr. Xu’s group published an article entitled “Cathelicidin antimicrobial peptides suppress EV71 infection via regulating antiviral response and inhibiting viral binding” in Antiviral Research.
Antimicrobial peptides (AMPs) are important components of innate immunity with microbicidal properties and immunoregulatory functions in host defense. Apart from the direct bactericidal activities and diverse immunomodulatory functions, LL-37 and CRAMP were recently demonstrated to have broad antiviral activities against enveloped virus. But the antiviral mechanism of LL-37 and CRAMP against non-enveloped viruses remain to be elucidated.
Our results found that (1) CRAMP expression was induced by EV71 inoculation in newborn ICR mice; (2) LL37 and CRAMP obviously reduced CPE caused by EV71 infection in human astrocytes; (3) LL37 and CRAMP efficiently inhibited EV71 replication; (4) LL-37 and CRAMP did not directly inactivate EV71 virons; (5) LL-37 and CRAMP markedly elicited IFN-β expression in human astrocytes; (6) LL-37 and CRAMP significantly inhibited IL-6 production in human astrocytes post EV71 infection; and (7) LL-37 and CRAMP directly inhibited the binding of EV71 to human astrocytes. Our findings demonstrated that cathelicidin antimicrobial peptides markedly enhanced type I interferon response in human astrocytes and inhibited viral binding to human astrocytes, in turn reduced EV71 replication and markedly inhibited proinflammatory cytokine production. Our work provides potent candidates for peptide drug development against EV71 infection.
Jie Yu, Yue Dai, and Yuxuan Fu are co-first authors. Min Li, Kezhen Wang are contributing authors. Dr. Wei Xu, and Lin Wei are co-corresponding authors. This work was supported by a Project Funded by National Natural Science Foundation of China (31870868, 31900679), and Key Research & Development Plan in Social Development of Jiangsu Province (BE2020652).