Toll-like receptor 3 is involved in detection of enterovirus a71 infection and targeted by viral 2a protease

Kuan Ru Chen, Chun Keung Yu, Szu Hao Kung, Shun Hua Chen, Chuan Fa Chang, Tzu Chuan Ho, Yi Ping Lee, Hung Chuan Chang, Lan Yin Huang, Shih Yen Lo, Jui Chung Chang, Pin Ling

研究成果: Article

3 引文 (Scopus)

摘要

Enterovirus A71 (EV-A71) has emerged as a major pathogen causing hand, foot, and mouth disease, as well as neurological disorders. The host immune response affects the outcomes of EV-A71 infection, leading to either resolution or disease progression. However, the mechanisms of how the mammalian innate immune system detects EV-A71 infection to elicit antiviral immunity remain elusive. Here, we report that the Toll-like receptor 3 (TLR3) is a key viral RNA sensor for sensing EV-A71 infection to trigger antiviral immunity. Expression of TLR3 in HEK293 cells enabled the cells to sense EV-A71 infection, leading to type I, IFN-mediated antiviral immunity. Viral double-stranded RNA derived from EV-A71 infection was a key ligand for TLR3 detection. Silencing of TLR3 in mouse and human primary immune cells impaired the activation of IFN-β upon EV-A71 infection, thus reinforcing the importance of the TLR3 pathway in defending against EV-A71 infection. Our results further demonstrated that TLR3 was a target of EV-A71 infection. EV-A71 protease 2A was implicated in the downregulation of TLR3. Together, our results not only demonstrate the importance of the TLR3 pathway in response to EV-A71 infection, but also reveal the involvement of EV-A71 protease 2A in subverting TLR3-mediated antiviral defenses.

原文English
文章編號689
期刊Viruses
10
發行號12
DOIs
出版狀態Published - 2018 十二月

指紋

Toll-Like Receptor 3
Enterovirus Infections
Peptide Hydrolases
Antiviral Agents
Enterovirus
Immunity
Viral RNA
Hand, Foot and Mouth Disease
Double-Stranded RNA
HEK293 Cells
Nervous System Diseases
Disease Progression
Immune System
Down-Regulation
Ligands

All Science Journal Classification (ASJC) codes

  • Infectious Diseases
  • Virology

引用此文

Chen, Kuan Ru ; Yu, Chun Keung ; Kung, Szu Hao ; Chen, Shun Hua ; Chang, Chuan Fa ; Ho, Tzu Chuan ; Lee, Yi Ping ; Chang, Hung Chuan ; Huang, Lan Yin ; Lo, Shih Yen ; Chang, Jui Chung ; Ling, Pin. / Toll-like receptor 3 is involved in detection of enterovirus a71 infection and targeted by viral 2a protease. 於: Viruses. 2018 ; 卷 10, 編號 12.
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title = "Toll-like receptor 3 is involved in detection of enterovirus a71 infection and targeted by viral 2a protease",
abstract = "Enterovirus A71 (EV-A71) has emerged as a major pathogen causing hand, foot, and mouth disease, as well as neurological disorders. The host immune response affects the outcomes of EV-A71 infection, leading to either resolution or disease progression. However, the mechanisms of how the mammalian innate immune system detects EV-A71 infection to elicit antiviral immunity remain elusive. Here, we report that the Toll-like receptor 3 (TLR3) is a key viral RNA sensor for sensing EV-A71 infection to trigger antiviral immunity. Expression of TLR3 in HEK293 cells enabled the cells to sense EV-A71 infection, leading to type I, IFN-mediated antiviral immunity. Viral double-stranded RNA derived from EV-A71 infection was a key ligand for TLR3 detection. Silencing of TLR3 in mouse and human primary immune cells impaired the activation of IFN-β upon EV-A71 infection, thus reinforcing the importance of the TLR3 pathway in defending against EV-A71 infection. Our results further demonstrated that TLR3 was a target of EV-A71 infection. EV-A71 protease 2A was implicated in the downregulation of TLR3. Together, our results not only demonstrate the importance of the TLR3 pathway in response to EV-A71 infection, but also reveal the involvement of EV-A71 protease 2A in subverting TLR3-mediated antiviral defenses.",
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Toll-like receptor 3 is involved in detection of enterovirus a71 infection and targeted by viral 2a protease. / Chen, Kuan Ru; Yu, Chun Keung; Kung, Szu Hao; Chen, Shun Hua; Chang, Chuan Fa; Ho, Tzu Chuan; Lee, Yi Ping; Chang, Hung Chuan; Huang, Lan Yin; Lo, Shih Yen; Chang, Jui Chung; Ling, Pin.

於: Viruses, 卷 10, 編號 12, 689, 12.2018.

研究成果: Article

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AU - Chen, Kuan Ru

AU - Yu, Chun Keung

AU - Kung, Szu Hao

AU - Chen, Shun Hua

AU - Chang, Chuan Fa

AU - Ho, Tzu Chuan

AU - Lee, Yi Ping

AU - Chang, Hung Chuan

AU - Huang, Lan Yin

AU - Lo, Shih Yen

AU - Chang, Jui Chung

AU - Ling, Pin

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N2 - Enterovirus A71 (EV-A71) has emerged as a major pathogen causing hand, foot, and mouth disease, as well as neurological disorders. The host immune response affects the outcomes of EV-A71 infection, leading to either resolution or disease progression. However, the mechanisms of how the mammalian innate immune system detects EV-A71 infection to elicit antiviral immunity remain elusive. Here, we report that the Toll-like receptor 3 (TLR3) is a key viral RNA sensor for sensing EV-A71 infection to trigger antiviral immunity. Expression of TLR3 in HEK293 cells enabled the cells to sense EV-A71 infection, leading to type I, IFN-mediated antiviral immunity. Viral double-stranded RNA derived from EV-A71 infection was a key ligand for TLR3 detection. Silencing of TLR3 in mouse and human primary immune cells impaired the activation of IFN-β upon EV-A71 infection, thus reinforcing the importance of the TLR3 pathway in defending against EV-A71 infection. Our results further demonstrated that TLR3 was a target of EV-A71 infection. EV-A71 protease 2A was implicated in the downregulation of TLR3. Together, our results not only demonstrate the importance of the TLR3 pathway in response to EV-A71 infection, but also reveal the involvement of EV-A71 protease 2A in subverting TLR3-mediated antiviral defenses.

AB - Enterovirus A71 (EV-A71) has emerged as a major pathogen causing hand, foot, and mouth disease, as well as neurological disorders. The host immune response affects the outcomes of EV-A71 infection, leading to either resolution or disease progression. However, the mechanisms of how the mammalian innate immune system detects EV-A71 infection to elicit antiviral immunity remain elusive. Here, we report that the Toll-like receptor 3 (TLR3) is a key viral RNA sensor for sensing EV-A71 infection to trigger antiviral immunity. Expression of TLR3 in HEK293 cells enabled the cells to sense EV-A71 infection, leading to type I, IFN-mediated antiviral immunity. Viral double-stranded RNA derived from EV-A71 infection was a key ligand for TLR3 detection. Silencing of TLR3 in mouse and human primary immune cells impaired the activation of IFN-β upon EV-A71 infection, thus reinforcing the importance of the TLR3 pathway in defending against EV-A71 infection. Our results further demonstrated that TLR3 was a target of EV-A71 infection. EV-A71 protease 2A was implicated in the downregulation of TLR3. Together, our results not only demonstrate the importance of the TLR3 pathway in response to EV-A71 infection, but also reveal the involvement of EV-A71 protease 2A in subverting TLR3-mediated antiviral defenses.

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