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Cyclophilin A Associates with Enterovirus-71 Virus Capsid and Plays an Essential Role in Viral Infection as an Uncoating Regulator


Enterovirus 71 (EV71) is the major causative agent of hand-foot-and-mouth disease (HFMD) in Asia-Pacific region and caused over one million infection cases and nine hundred deaths in the year of 2010 in China mainland. EV71 is known to infect the young children for the sake of their undeveloped immune system. Unlike other Enterovirus (e.g. coxsackievirus), EV71 could cause severe aseptic meningitis, encephalitis, myocarditis, and acute flaccid paralysis, thus leading to high fatality rates. There is no clinically applied therapeutics. In this work, we used CypA inhibitors as bioprobes to show that CypA played an essential role in EV71 proliferation. We also elucidated the mechanism by which CypA interacted with the EV71 VP1 H-I loop and functioned as an uncoating regulator in EV71 entry step. Since there are several non-immunosuppressive CypA inhibitors, e.g. NIM-811 and Debio-025, have been reported to show antiviral potency, our results provide a potential way to discover clinical therapeutics against EV71 infection.


Vyšlo v časopise: Cyclophilin A Associates with Enterovirus-71 Virus Capsid and Plays an Essential Role in Viral Infection as an Uncoating Regulator. PLoS Pathog 10(10): e32767. doi:10.1371/journal.ppat.1004422
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004422

Souhrn

Enterovirus 71 (EV71) is the major causative agent of hand-foot-and-mouth disease (HFMD) in Asia-Pacific region and caused over one million infection cases and nine hundred deaths in the year of 2010 in China mainland. EV71 is known to infect the young children for the sake of their undeveloped immune system. Unlike other Enterovirus (e.g. coxsackievirus), EV71 could cause severe aseptic meningitis, encephalitis, myocarditis, and acute flaccid paralysis, thus leading to high fatality rates. There is no clinically applied therapeutics. In this work, we used CypA inhibitors as bioprobes to show that CypA played an essential role in EV71 proliferation. We also elucidated the mechanism by which CypA interacted with the EV71 VP1 H-I loop and functioned as an uncoating regulator in EV71 entry step. Since there are several non-immunosuppressive CypA inhibitors, e.g. NIM-811 and Debio-025, have been reported to show antiviral potency, our results provide a potential way to discover clinical therapeutics against EV71 infection.


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Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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PLOS Pathogens


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