The uncoating of EV71 in mature late endosomes requires CD-M6PR
Document Type
Article
Publication Date
9-1-2022
Abstract
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.
Keywords
EV71, Late endosomes, Mannose 6-phosphate receptor, Uncoating, SCARB2
Divisions
biomedsc,pathology
Funders
Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Japan Society for the Promotion of Science [Grant No: 25460583],Naito Memorial Foundation,High Impact Research from the Ministry of Higher Education, Malaysia government [Grant No: UM.C/625/1/HIR/MOHE/MED/06],Wellcome Trust [Grant No: 223022/Z/21/Z]
Publication Title
Biology Open
Volume
11
Issue
9
Publisher
Company Biologists Ltd
Publisher Location
BIDDER BUILDING, STATION RD, HISTON, CAMBRIDGE CB24 9LF, ENGLAND