An Amphibian Host Defense Peptide Is Virucidal for Human H1 Hemagglutinin-Bearing Influenza Viruses

被引:77
作者
Holthausen, David J. [1 ]
Lee, Song Hee [1 ]
Kumar, Vineeth T. V. [2 ]
Bouvier, Nicole M. [3 ]
Krammer, Florian [3 ]
Ellebedy, Ali H. [1 ]
Wrammert, Jens [1 ]
Lowen, Anice C. [1 ]
George, Sanil [2 ]
Pillai, Madhavan Radhakrishna [2 ]
Jacob, Joshy [1 ]
机构
[1] Emory Univ, Yerkes Natl Primate Ctr, Emory Vaccine Ctr, 954 Gatewood Rd, Atlanta, GA 30329 USA
[2] Rajiv Gandhi Ctr Biotechnol, Thiruvananthapuram, Kerala, India
[3] Icahn Sch Med Mt Sinai, Dept Microbiol, One Gustave L Levy Pl,Box 1124, New York, NY 10029 USA
关键词
HERPES-SIMPLEX-VIRUS; ANTIMICROBIAL PEPTIDES; THERAPEUTIC APPLICATIONS; ANTIVIRAL ACTIVITY; ANTIBODIES; SKIN; INACTIVATION; MECHANISM; PROSPECTS; VACCINES;
D O I
10.1016/j.immuni.2017.03.018
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Although vaccines confer protection against influenza A viruses, antiviral treatment becomes the first line of defense during pandemics because there is insufficient time to produce vaccines. Current antiviral drugs are susceptible to drug resistance, and developing new antivirals is essential. We studied host defense peptides from the skin of the South Indian frog and demonstrated that one of these, which we named "urumin," is virucidal for H1 hemagglutinin-bearing human influenza A viruses. This peptide specifically targeted the conserved stalk region of H1 hemagglutinin and was effective against drug-resistant H1 influenza viruses. Using electron microscopy, we showed that this peptide physically destroyed influenza virions. It also protected naive mice from lethal influenza infection. Urumin represents a unique class of anti-influenza virucide that specifically targets the hemagglutinin stalk region, similar to targeting of antibodies induced by universal influenza vaccines. Urumin therefore has the potential to contribute to first-line anti-viral treatments during influenza outbreaks.
引用
收藏
页码:587 / 595
页数:9
相关论文
共 44 条
[1]   In vitro antiviral activity of dermaseptins against herpes simplex virus type-1 [J].
Belaid, A ;
Aouni, M ;
Khelifa, R ;
Trabelsi, A ;
Jemmali, M ;
Hani, K .
JOURNAL OF MEDICAL VIROLOGY, 2002, 66 (02) :229-234
[2]   PEPTIDES FROM FROG-SKIN [J].
BEVINS, CL ;
ZASLOFF, M .
ANNUAL REVIEW OF BIOCHEMISTRY, 1990, 59 :395-414
[3]   Enhanced Mammalian Transmissibility of Seasonal Influenza A/H1N1 Viruses Encoding an Oseltamivir-Resistant Neuraminidase [J].
Bouvier, Nicole M. ;
Rahmat, Saad ;
Pica, Natalie .
JOURNAL OF VIROLOGY, 2012, 86 (13) :7268-7279
[4]   Role of lipid-bound peptidoglycan precursors in the formation of pores by nisin, epidermin and other lantibiotics [J].
Brötz, H ;
Josten, M ;
Wiedemann, I ;
Schneider, U ;
Götz, F ;
Bierbaum, G ;
Sahl, HG .
MOLECULAR MICROBIOLOGY, 1998, 30 (02) :317-327
[5]   Inactivation of viruses infecting ectothermic animals by amphibian and piscine antimicrobial peptides [J].
Chinchar, VG ;
Bryan, L ;
Silphadaung, U ;
Noga, E ;
Wade, D ;
Rollins-Smith, L .
VIROLOGY, 2004, 323 (02) :268-275
[6]   Potential therapeutic applications of multifunctional host-defense peptides from frog skin as anti-cancer, anti-viral, immunomodulatory, and anti-diabetic agents [J].
Conlon, J. Michael ;
Mechkarska, Milena ;
Lukic, Miodrag L. ;
Flatt, Peter R. .
PEPTIDES, 2014, 57 :67-77
[7]   ASSEMBLY OF INFLUENZA HEMAGGLUTININ TRIMERS AND ITS ROLE IN INTRACELLULAR-TRANSPORT [J].
COPELAND, CS ;
DOMS, RW ;
BOLZAU, EM ;
WEBSTER, RG ;
HELENIUS, A .
JOURNAL OF CELL BIOLOGY, 1986, 103 (04) :1179-1191
[8]  
Anonymous, 2006, Morbidity and Mortality Weekly Report, V55, P1
[9]   Broadly neutralizing antibodies against influenza virus and prospects for universal therapies [J].
Ekiert, Damian C. ;
Wilson, Ian A. .
CURRENT OPINION IN VIROLOGY, 2012, 2 (02) :134-141
[10]  
Fiore Anthony E., 2011, Morbidity and Mortality Weekly Report, V60, P1