期刊
BIOLOGY OPEN
卷 11, 期 9, 页码 -出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/bio.059469
关键词
EV71; Late endosomes; Mannose 6-phosphate receptor; Uncoating; SCARB2
类别
资金
- Japan Society for the Promotion of Science [25460583]
- Naito Foundation
- High Impact Research from the Ministry of Higher Education, Malaysia government [UM.C/625/1/HIR/MOHE/MED/06 (UM.0000064/HIR.C1)]
- Wellcome Trust [107116/Z/15/Z, 223022/Z/21/Z]
- UK Dementia Research Institute Foundation [UKDRI-1005]
- Naito Foundation Subsidy for Female Researchers after Maternity Leave
- Tokyo Metropolitan Institute of Medical Science
- Wellcome Trust [223022/Z/21/Z] Funding Source: Wellcome Trust
Recent research has shown that EV71, a causative agent of hand-foot-and-mouth disease, undergoes efficient uncoating in late endosomes containing hSCARB2, M6PR, RAB9, bis(monoacylglycero)phosphate, and LAMP2. The autophagic pathway does not play a critical role in EV71 uncoating, and cation-dependent M6PR is likely to be important for this process.
Enterovirus 71 (EV71) is one of the causative agents of handfoot-and-mouth disease, which in some circumstances could lead to severe neurological diseases. Despite of its importance for human health, little is known about the early stages of EV71 infection. EV71 starts uncoating with its receptor, human scavenger receptor B2 (hSCARB2), at low pH. We show that EV71 was not targeted to lysosomes in human rhabdomyosarcoma cells overexpressing hSCARB2 and that the autophagic pathway is not essential for EV71 productive uncoating. Instead, EV71 was efficiently uncoated 30 min after infection in late endosomes (LEs) containing hSCARB2, mannose-6-phosphate receptor (M6PR), RAB9, bis( monoacylglycero) phosphate and lysosomal associated membrane protein 2 (LAMP2). Furthering the notion that mature LEs are crucial for EV71 uncoating, cation-dependent (CD)-M6PR knockdown impairs EV71 infection. Since hSCARB2 interacts with cation- independent (CI)-M6PR through M6Pbinding sites and CD-M6PR also harbor a M6P-binding site, CD-M6PR is likely to play important roles in EV71 uncoating in LEs.
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