antiviral activity and increased host defense against influenza infection elicited by the human cathelicidin ll-37抗病毒活性和增加宿主防御流感感染人类抗菌肽ll-37引起的.pdf

Antiviral Activity and Increased Host Defense against Influenza Infection Elicited by the Human Cathelicidin LL-37 1¤ 2 3 4 1 2 Peter G. Barlow , Pavel Svoboda , Annie Mackellar , Anthony A. Nash , Ian A. York , Jan Pohl , 3. 1 . Donald J. Davidson , Ruben O. Donis * 1 Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America, 2 Biotechnology Core Facility Branch, Division of Scientific Resources, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America, 3 MRC Centre for Inflammation Research, Queens Medical Research Institute, The University of Edinburgh, Edinburgh, United Kingdom, 4 The Roslin Institute and Centre for Infectious Diseases, University of Edinburgh, Edinburgh, United Kingdom Abstract The extensive world-wide morbidity and mortality caused by influenza A viruses highlights the need for new insights into the host immune response and novel treatment approaches. Cationic Host Defense Peptides (CHDP, also known as antimicrobial peptides), which include cathelicidins and defensins, are key components of the innate immune system that are upregulated during infection and inflammation. Cathelicidins have immunomodulatory and anti-viral effects, but their impact on influenza virus infection has not been previously assessed. We therefore evaluated the effect of cathelicidin peptides on disease caused by influenza A virus in mice. The human cathelicidin, LL-37, and the murine cathelicidin, mCRAMP, demonstrated significant anti-viral activity in vivo, reducing disease severity and viral replication in infected mice to a similar extent as the well- characterized influenza viru