KREMEN1 Is a Host Entry Receptor for a Major Group of Enteroviruses

Human type A Enteroviruses (EV-As) cause diseases ranging from hand-foot-and-mouth disease to poliomyelitis-like disease. Although cellular receptors are identified for some EV-As, they remain elusive for the majority of EV-As. We identify the cell surface molecule KREMEN1 as an entry receptor for c...

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Vydáno v:Cell host & microbe Ročník 23; číslo 5; s. 636
Hlavní autoři: Staring, Jacqueline, van den Hengel, Lisa G, Raaben, Matthijs, Blomen, Vincent A, Carette, Jan E, Brummelkamp, Thijn R
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 09.05.2018
Témata:
Enterovirus type A
receptor
host factor
KREMEN
coxsackievirus
haploid genetic screen
WNT signaling
ISSN:1934-6069, 1934-6069
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Shrnutí:Human type A Enteroviruses (EV-As) cause diseases ranging from hand-foot-and-mouth disease to poliomyelitis-like disease. Although cellular receptors are identified for some EV-As, they remain elusive for the majority of EV-As. We identify the cell surface molecule KREMEN1 as an entry receptor for coxsackievirus A10 (CV-A10). Whereas loss of KREMEN1 renders cells resistant to CV-A10 infection, KREMEN1 overexpression enhances CV-A10 binding to the cell surface and increases susceptibility to infection, indicating that KREMEN1 is a rate-limiting factor for CV-A10 infection. Furthermore, the extracellular domain of KREMEN1 binds CV-A10 and functions as a neutralizing agent during infection. Kremen-deficient mice are resistant to CV-A10-induced lethal paralysis, emphasizing the relevance of Kremen for infection in vivo. KREMEN1 is also essential for infection by a phylogenetic and pathogenic related group of EV-As. Collectively these findings highlight the importance of KREMEN1 for these emerging pathogens and its potential as an antiviral therapeutic target.
Bibliografie:ObjectType-Article-1
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content type line 23
ISSN:1934-6069
1934-6069
DOI:10.1016/j.chom.2018.03.019