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Binding of cellular nucleolin with the viral core RNA G-quadruplex structure suppresses HCV replication.

Abstract：

:Hepatitis C virus (HCV) infection is a major cause of human chronic liver disease and hepatocellular carcinoma. G-quadruplex (G4) is an important four-stranded secondary structure of nucleic acids. Recently, we discovered that the core gene of HCV contains a G4 RNA structure; however, the interaction between the HCV core RNA G4 and host cellular proteins, and the roles of the HCV core RNA G4 in HCV infection and pathogenesis remain elusive. Here, we identified a cellular protein, nucleolin (NCL), which bound and stabilized the HCV core RNA G4 structure. We demonstrated the direct interaction and colocalization between NCL and wild-type core RNA G4 at both in vitro and in cell physiological conditions of the alive virus; however no significant interaction was found between NCL and G4-modified core RNA. NCL is also associated with HCV particles. HCV infection induced NCL mRNA and protein expression, while NCL suppressed wild-type viral replication and expression, but not G4-modified virus. Silencing of NCL greatly enhanced viral RNA replication. Our findings provide new insights that NCL may act as a host factor for anti-viral innate immunity, and binding of cellular NCL with the viral core RNA G4 structure is involved in suppressing HCV replication.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Bian WX,Xie Y,Wang XN,Xu GH,Fu BS,Li S,Long G,Zhou X,Zhang XL

doi

10.1093/nar/gky1177

subject

Has Abstract

pub_date

2019-01-10 00:00:00

pages

56-68

issue

1

eissn

0305-1048

issn

1362-4962

pii

5193559

journal_volume

47

pub_type

杂志文章

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