Type I interferons protect mice against enterovirus 71 infection.
In this study, the contribution of type I interferons (IFNs) to protection against infection with enterovirus 71 (EV71) was investigated using a murine model where the virus was administrated to neonatal Institute of Cancer Research (ICR) mice by either the intraperitoneal (i.p.) or the oral route. In i.p. inoculated mice, post-infection treatment of dexamethasone (5 mg kg(-1) at 2 or 3 days after infection) exacerbated clinical symptoms and increased the tissue viral titre. In contrast, polyriboinosinic : polyribocytidylic acid [poly(I : C); 10 or 100 microg per mouse at 12 h before infection], a potent IFN inducer, improved the survival rate and decreased the tissue viral titres after EV71 challenge, which correlated with an increase in serum IFN-alpha concentration, the percentage of dendritic cells, their expression of major histocompatibility complex class II molecule and IFN-alpha in spleen. Treatment with a neutralizing antibody for type I IFNs (10(4) neutralizing units per mouse, 6 h before and 12 h after infection) resulted in frequent deaths and higher tissue viral load in infected mice compared with control mice. In contrast, an early administration of recombinant mouse IFN-alphaA (10(4) U per mouse for 3 days starting at 0, 1 or 3 days after infection) protected the mice against EV71 infection. In vitro analysis of virus-induced death in three human cell lines showed that human type I IFNs exerted a direct protective effect on EV71. It was concluded that type I IFNs play an important role in controlling EV71 infection and replication.
Liu
Ming-Liang
ML
Department of Microbiology & Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan 70101, Republic of China.
Lee
Yi-Ping
YP
Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan 70101, Republic of China.
Wang
Ya-Fang
YF
Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan 70101, Republic of China.
Lei
Huan-Yao
HY
Department of Microbiology & Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan 70101, Republic of China.
Liu
Ching-Chuan
CC
Department of Pediatrics, College of Medicine, National Cheng Kung University, Tainan, Taiwan 70101, Republic of China.
Wang
Shih-Min
SM
Department of Pediatrics, College of Medicine, National Cheng Kung University, Tainan, Taiwan 70101, Republic of China.
Su
Ih-Jen
IJ
Department of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan 70101, Republic of China.
Wang
Jen-Reng
JR
Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan 70101, Republic of China.
Yeh
Trai-Ming
TM
Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan 70101, Republic of China.
Chen
Shun-Hua
SH
Department of Microbiology & Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan 70101, Republic of China.
Yu
Chun-Keung
CK
Department of Microbiology & Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan 70101, Republic of China.
D000818:Animals; D000906:Antibodies / Q000276:immunology; D000998:Antiviral Agents / Q000494:pharmacology*; D039521:CD11c Antigen / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D003713:Dendritic Cells; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D004770:Enterovirus / Q000187:drug effects; D004769:Enterovirus Infections / Q000188:drug therapy* / Q000517:prevention & control*; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D007370:Interferon Type I / Q000276:immunology* / Q000494:pharmacology*; D017493:Leukocyte Common Antigens / Q000032:analysis; D051379:Mice; D008813:Mice, Inbred ICR; D011070:Poly I-C / Q000494:pharmacology; D011119:Polynucleotides / Q000494:pharmacology; D013154:Spleen / Q000276:immunology
D000906:Antibodies; D000998:Antiviral Agents; D039521:CD11c Antigen; D016827:CD8 Antigens; D000949:Histocompatibility Antigens Class II; D007370:Interferon Type I; D011119:Polynucleotides; D003907:Dexamethasone; D017493:Leukocyte Common Antigens; D011070:Poly I-C