Type I interferons protect mice against enterovirus 71 infection

• Published in: Journal of general virology Vol. 86; no. 12; pp. 3263 - 3269
• Main Authors: Liu, Ming-Liang, Lee, Yi-Ping, Wang, Ya-Fang, Lei, Huan-Yao, Liu, Ching-Chuan, Wang, Shih-Min, Su, Ih-Jen, Wang, Jen-Reng, Yeh, Trai-Ming, Chen, Shun-Hua, Yu, Chun-Keung
• Format: Journal Article
• Language: English
• Published: Reading Soc General Microbiol 01.12.2005; Society for General Microbiology
• Subjects: Animals; Antibodies - immunology; Antiviral Agents - pharmacology; Biological and medical sciences; CD11c Antigen - analysis; CD8 Antigens - analysis; Cell Line; Cytopathogenic Effect, Viral - drug effects; Dendritic Cells; Dexamethasone - pharmacology; Disease Models, Animal; Enterovirus; Enterovirus - drug effects; Enterovirus Infections - drug therapy; Enterovirus Infections - prevention & control; Fundamental and applied biological sciences. Psychology; Histocompatibility Antigens Class II - analysis; Humans; Interferon Type I - immunology; Interferon Type I - pharmacology; Leukocyte Common Antigens - analysis; Mice; Mice, Inbred ICR; Microbiology; Miscellaneous; Poly I-C - pharmacology; Polynucleotides - pharmacology; Spleen - immunology; Virology; Virus; Vertebrata; Mammalia; Microbiology; Mouse; Picornaviridae; Rodentia; Enterovirus; Interferon; Virology
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/vir.0.81195-0

1 Department of Microbiology & Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan 70101, Republic of China 2 Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan 70101, Republic of China 3 Department of Pediatrics, College of Medicine, National Cheng Kung University, Tainan, Taiwan 70101, Republic of China 4 Department of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan 70101, Republic of China 5 Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan 70101, Republic of China Correspondence Chun-Keung Yu dckyu{at}mail.ncku.edu.tw 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 µg 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- concentration, the percentage of dendritic cells, their expression of major histocompatibility complex class II molecule and IFN- 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- A (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.