MiR-127-5p Is A Negative Regulator Of Enterovirus 71 Replication By Directly Targeting SCARB2

Hand,foot and mouth disease(HFMD)is a highly contagious viral infection affecting young children during the spring to fall seasons.The clinical spectrum of HFMD is wide,ranging from a mild and self-limiting disease to aseptic meningitis,poliomyelitis-like acute flaccid paralysis,brainstem encephalitis,and other rare fatal manifestations with high fatality rates and severe sequelae.HFMD is most commonly caused by infection with coxsackievirus A16,and secondly by enterovirus 71(EV71).Importantly,HFMD caused by EV71 tends to be associated with fatal complications.EV71,a positive single stranded RNA virus belonging to the family of Picornaviridae,was first isolated from patients with neurological diseases.EV71 infections begin with the binding of cellular receptors of the host cell,which were demonstrated to be human scavenger receptor class B member 2(SCARB2)expressed extensively in tissues.As a receptor for all strains of EV71,SCARB2 is capable of mediating viral binding,internalization and uncoating,and is shown to play a crucial role in the early steps of EV71 infection.MicroRNAs(miRNAs)are a class of highly conserved noncoding RNA oligonucleotides of 21 to 22 nt that are found in animals,plants and viruses.These small RNAs primarily regulate the expression of specific genes by binding to complimentary sequences at target mRNAs to modulate their translation or stability.There are hundreds of miRNA-encoding genes in humans,which regulate protein-encoding genes.Recently,miRNAs have been noted to be a key effector molecules in the complex interaction network between virus and host,either by targeting cellular factors used for virus replication or by directly targeting viral mRNAs.This study aimed at elucidating whether and how EV71 infection is regulated by miR-127-5p.Here,we found that a cellular microRNA,miR-127-5p,can downregulate the expression of SCARB2,a main receptor of EV71,by targeting two potential sites in its 3’ UTR region and inhibit EV71 infection.Meanwhile,miR-127-5p expression was upregulated during EV71 infection.Notably,transfecting cells with miR-127-5p mimics led to a significant decrease in viral replication,while inhibition of endogenous miR-127-5p facilitated viral replication.Furthermore,our evidence showed that miR-127-5p didn’t affect post-entry viral replication.Taken together,these results indicated that miR-127-5p inhibited EV71 replication by targeting the SCARB2 mRNA.