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论文题目: Type I Interferons Triggered through the Toll-Like Receptor 3-TRIF Pathway Control Coxsackievirus A16 Infection in Young Mice
英文论文题目: Type I Interferons Triggered through the Toll-Like Receptor 3-TRIF Pathway Control Coxsackievirus A16 Infection in Young Mice
第一作者: Yang, JH; Yang, CF; Guo, NN; Zhu, K; Luo, KM; Zhang, N; Zhao, H; Cui, Y; Chen, L; Wang, HY; Gu, J; Ge, BX; Qin, CF; Leng, QB
英文第一作者: Yang, JH; Yang, CF; Guo, NN; Zhu, K; Luo, KM; Zhang, N; Zhao, H; Cui, Y; Chen, L; Wang, HY; Gu, J; Ge, BX; Qin, CF; Leng, QB
联系作者: Leng, QB (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Pasteur Shanghai, Key Lab Mol Virol & Immunol, Shanghai, Peoples R China.
英文联系作者: Leng, QB (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Pasteur Shanghai, Key Lab Mol Virol & Immunol, Shanghai, Peoples R China.
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发表年度: 2015
卷: 89
期: 21
页码: 10860-10867
摘要: Coxsackievirus A16 (CVA16) is one of the major etiological agents of hand, foot, and mouth disease (HFMD) in children. The host defense mechanisms against CVA16 infection remain almost entirely unknown. Unlike previous observations with enterovirus 71 (EV71) infection, here we show that gamma interferon (IFN-gamma) or invariant NK T cell deficiency does not affect disease development or the survival of CVA16-infected mice. In contrast, type I interferon receptor deficiency resulted in the development of more severe disease in mice, and the mice had a lower survival rate than wild-type mice. Similarly, a deficiency of Toll-like receptor 3 (TLR3) and TRIF, but not other pattern recognition receptors, led to the decreased survival of CVA16-infected mice. TLR3-TRIF signaling was indispensable for the induction of type I interferons during CVA16 infection in mice and protected young mice from disease caused by the infection. In particular, TRIF-mediated immunity was critical for preventing CVA16 replication in the neuronal system before disease occurred. IFN-beta treatment was also found to compensate for TRIF deficiency in mice and decreased the disease severity in and mortality of CVA16-infected mice. Altogether, type I interferons induced by TLR3-TRIF signaling mediate protective immunity against CVA16 infection. These findings may shed light on therapeutic strategies to combat HFMD caused by CVA16 infection. IMPORTANCE Hand, foot, and mouth disease (HFMD) is a major threat to public health in the Asia-Pacific region. Both CVA16 and EV71 are major pathogens that are responsible for HFMD. The majority of research efforts have focused on the more virulent EV71, but little has been done with CVA16. Thus far, host immune responses to CVA16 infection have not yet been elucidated. The present study discovered an initial molecular mechanism underlying host protective immunity against CVA16 infection, providing the first explanation for why CVA16 and EV71 cause different clinical outcomes upon infection of humans. Therefore, different therapeutic strategies should be developed to treat HFMD cases caused by these two viruses.
英文摘要: Coxsackievirus A16 (CVA16) is one of the major etiological agents of hand, foot, and mouth disease (HFMD) in children. The host defense mechanisms against CVA16 infection remain almost entirely unknown. Unlike previous observations with enterovirus 71 (EV71) infection, here we show that gamma interferon (IFN-gamma) or invariant NK T cell deficiency does not affect disease development or the survival of CVA16-infected mice. In contrast, type I interferon receptor deficiency resulted in the development of more severe disease in mice, and the mice had a lower survival rate than wild-type mice. Similarly, a deficiency of Toll-like receptor 3 (TLR3) and TRIF, but not other pattern recognition receptors, led to the decreased survival of CVA16-infected mice. TLR3-TRIF signaling was indispensable for the induction of type I interferons during CVA16 infection in mice and protected young mice from disease caused by the infection. In particular, TRIF-mediated immunity was critical for preventing CVA16 replication in the neuronal system before disease occurred. IFN-beta treatment was also found to compensate for TRIF deficiency in mice and decreased the disease severity in and mortality of CVA16-infected mice. Altogether, type I interferons induced by TLR3-TRIF signaling mediate protective immunity against CVA16 infection. These findings may shed light on therapeutic strategies to combat HFMD caused by CVA16 infection. IMPORTANCE Hand, foot, and mouth disease (HFMD) is a major threat to public health in the Asia-Pacific region. Both CVA16 and EV71 are major pathogens that are responsible for HFMD. The majority of research efforts have focused on the more virulent EV71, but little has been done with CVA16. Thus far, host immune responses to CVA16 infection have not yet been elucidated. The present study discovered an initial molecular mechanism underlying host protective immunity against CVA16 infection, providing the first explanation for why CVA16 and EV71 cause different clinical outcomes upon infection of humans. Therefore, different therapeutic strategies should be developed to treat HFMD cases caused by these two viruses.
刊物名称: JOURNAL OF VIROLOGY
英文刊物名称: JOURNAL OF VIROLOGY
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学科: Virology
英文学科: Virology
影响因子: 4.439
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论文类别: Article
英文论文类别: Article
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