Please use this identifier to cite or link to this item: https://doi.org/10.1038/emi.2016.56
Title: Cooperative effect of the VP1 amino acids 98E, 145A and 169F in the productive infection of mouse cell lines by enterovirus 71 (BS strain)
Authors: Victorio, C.B 
Xu, Y
Ng, Q
Meng, T
Chow, V.T 
Chua, K.B
Keywords: amino acid
capsid protein
CD36 antigen
lysosome associated membrane protein
Scarb2 protein, mouse
VP1 protein, Foot-and-mouth disease virus
VP2 protein, Foot-and-mouth disease virus
amino acid sequence
amino acid substitution
animal
cell line
chemistry
Chlorocebus aethiops
Enterovirus A
genetics
metabolism
mouse
mutation
NIH 3T3 cell line
physiology
reverse genetics
site directed mutagenesis
tumor cell line
Vero cell line
Amino Acid Sequence
Amino Acid Substitution
Amino Acids
Animals
Antigens, CD36
Capsid Proteins
Cell Line
Cell Line, Tumor
Cercopithecus aethiops
Enterovirus A, Human
Lysosome-Associated Membrane Glycoproteins
Mice
Mutagenesis, Site-Directed
Mutation
NIH 3T3 Cells
Reverse Genetics
Vero Cells
Issue Date: 2016
Citation: Victorio, C.B, Xu, Y, Ng, Q, Meng, T, Chow, V.T, Chua, K.B (2016). Cooperative effect of the VP1 amino acids 98E, 145A and 169F in the productive infection of mouse cell lines by enterovirus 71 (BS strain). Emerging microbes & infections 5 : e60. ScholarBank@NUS Repository. https://doi.org/10.1038/emi.2016.56
Abstract: Enterovirus 71 (EV71) is a neurotrophic virus that causes hand, foot and mouth disease (HFMD) and occasional neurological infection among children. It infects primate cells but not rodent cells, primarily due to the incompatibility between the virus and the expressed form of its receptor, scavenger receptor class B member 2 (SCARB2) protein, on rodent cells (mSCARB2). We previously generated adapted strains (EV71:TLLm and EV71:TLLmv) that were shown to productively infect primate and rodent cell lines and whose genomes exhibited a multitude of non-synonymous mutations compared with the EV71:BS parental virus. In this study, we aimed to identify mutations that are necessary for productive infection of murine cells by EV71:BS. Using reverse genetics and site-directed mutagenesis, we constructed EV71 infectious clones with specific mutations that generated amino acid substitutions in the capsid VP1 and VP2 proteins. We subsequently assessed the infection induced by clone-derived viruses (CDVs) in mouse embryonic fibroblast NIH/3T3 and murine neuroblastoma Neuro-2a cell lines. We found that the CDV:BS-VP1(K98E,E145A,L169F) with three substitutions in the VP1 protein-K98E, E145A and L169F-productively infected both mouse cell lines for at least three passages of the virus in murine cells. Moreover, the virus gained the ability to utilize the mSCARB2 protein to infect murine cell lines. These results demonstrate that the three VP1 residues cooperate to effectively interact with the mSCARB2 protein on murine cells and permit the virus to infect murine cells. Gain-of-function studies similar to the present work provide valuable insight into the mutational trajectory required for EV71 to infect new host cells previously non-susceptible to infection.
Source Title: Emerging microbes & infections
URI: https://scholarbank.nus.edu.sg/handle/10635/176522
ISSN: 2222-1751
DOI: 10.1038/emi.2016.56
Appears in Collections:Staff Publications
Elements

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1038_emi_2016_56.pdf5.1 MBAdobe PDF

OPEN

NoneView/Download

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.