Far upstream element binding protein 1 binds the internal ribosomal entry site of enterovirus 71 and enhances viral translation and viral growth

Peng Nien Huang, Jing Yi Lin, Nicolas Locker, Yu An Kung, Chuan Tien Hung, Jhao Yin Lin, Hsing I. Huang, Mei Ling Li, Shin Ru Shih

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Enterovirus 71 (EV71) is associated with severe neurological disorders in children, and has been implicated as the infectious agent in several large-scale outbreaks with mortalities. Upon infection, the viral RNA is translated in a cap-independent manner to yield a large polyprotein precursor. This mechanism relies on the presence of an internal ribosome entry site (IRES) element within the 5′-untranslated region. Virus-host interactions in EV71-infected cells are crucial in assisting this process. We identified a novel positive IRES trans-acting factor, far upstream element binding protein 1 (FBP1). Using binding assays, we mapped the RNA determinants within the EV71 IRES responsible for FBP1 binding and mapped the protein domains involved in this interaction. We also demonstrated that during EV71 infection, the nuclear protein FBP1 is enriched in cytoplasm where viral replication occurs. Moreover, we showed that FBP1 acts as a positive regulator of EV71 replication by competing with negative ITAF for EV71 IRES binding. These new findings may provide a route to new anti-viral therapy.

Original languageEnglish
Pages (from-to)9633-9648
Number of pages16
JournalNucleic Acids Research
Volume39
Issue number22
DOIs
Publication statusPublished - Dec 2011
Externally publishedYes

Fingerprint

Enterovirus
Carrier Proteins
Growth
Enterovirus Infections
Polyproteins
Trans-Activators
5' Untranslated Regions
Viral RNA
Nuclear Proteins
Nervous System Diseases
Protein Binding
Disease Outbreaks
Cytoplasm
RNA
Viruses
Mortality
Internal Ribosome Entry Sites
Infection

ASJC Scopus subject areas

  • Genetics

Cite this

Far upstream element binding protein 1 binds the internal ribosomal entry site of enterovirus 71 and enhances viral translation and viral growth. / Huang, Peng Nien; Lin, Jing Yi; Locker, Nicolas; Kung, Yu An; Hung, Chuan Tien; Lin, Jhao Yin; Huang, Hsing I.; Li, Mei Ling; Shih, Shin Ru.

In: Nucleic Acids Research, Vol. 39, No. 22, 12.2011, p. 9633-9648.

Research output: Contribution to journalArticle

Huang, Peng Nien ; Lin, Jing Yi ; Locker, Nicolas ; Kung, Yu An ; Hung, Chuan Tien ; Lin, Jhao Yin ; Huang, Hsing I. ; Li, Mei Ling ; Shih, Shin Ru. / Far upstream element binding protein 1 binds the internal ribosomal entry site of enterovirus 71 and enhances viral translation and viral growth. In: Nucleic Acids Research. 2011 ; Vol. 39, No. 22. pp. 9633-9648.
@article{6f3ce730328842a595f7cb98868b0eda,
title = "Far upstream element binding protein 1 binds the internal ribosomal entry site of enterovirus 71 and enhances viral translation and viral growth",
abstract = "Enterovirus 71 (EV71) is associated with severe neurological disorders in children, and has been implicated as the infectious agent in several large-scale outbreaks with mortalities. Upon infection, the viral RNA is translated in a cap-independent manner to yield a large polyprotein precursor. This mechanism relies on the presence of an internal ribosome entry site (IRES) element within the 5′-untranslated region. Virus-host interactions in EV71-infected cells are crucial in assisting this process. We identified a novel positive IRES trans-acting factor, far upstream element binding protein 1 (FBP1). Using binding assays, we mapped the RNA determinants within the EV71 IRES responsible for FBP1 binding and mapped the protein domains involved in this interaction. We also demonstrated that during EV71 infection, the nuclear protein FBP1 is enriched in cytoplasm where viral replication occurs. Moreover, we showed that FBP1 acts as a positive regulator of EV71 replication by competing with negative ITAF for EV71 IRES binding. These new findings may provide a route to new anti-viral therapy.",
author = "Huang, {Peng Nien} and Lin, {Jing Yi} and Nicolas Locker and Kung, {Yu An} and Hung, {Chuan Tien} and Lin, {Jhao Yin} and Huang, {Hsing I.} and Li, {Mei Ling} and Shih, {Shin Ru}",
year = "2011",
month = "12",
doi = "10.1093/nar/gkr682",
language = "English",
volume = "39",
pages = "9633--9648",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "22",

}

TY - JOUR

T1 - Far upstream element binding protein 1 binds the internal ribosomal entry site of enterovirus 71 and enhances viral translation and viral growth

AU - Huang, Peng Nien

AU - Lin, Jing Yi

AU - Locker, Nicolas

AU - Kung, Yu An

AU - Hung, Chuan Tien

AU - Lin, Jhao Yin

AU - Huang, Hsing I.

AU - Li, Mei Ling

AU - Shih, Shin Ru

PY - 2011/12

Y1 - 2011/12

N2 - Enterovirus 71 (EV71) is associated with severe neurological disorders in children, and has been implicated as the infectious agent in several large-scale outbreaks with mortalities. Upon infection, the viral RNA is translated in a cap-independent manner to yield a large polyprotein precursor. This mechanism relies on the presence of an internal ribosome entry site (IRES) element within the 5′-untranslated region. Virus-host interactions in EV71-infected cells are crucial in assisting this process. We identified a novel positive IRES trans-acting factor, far upstream element binding protein 1 (FBP1). Using binding assays, we mapped the RNA determinants within the EV71 IRES responsible for FBP1 binding and mapped the protein domains involved in this interaction. We also demonstrated that during EV71 infection, the nuclear protein FBP1 is enriched in cytoplasm where viral replication occurs. Moreover, we showed that FBP1 acts as a positive regulator of EV71 replication by competing with negative ITAF for EV71 IRES binding. These new findings may provide a route to new anti-viral therapy.

AB - Enterovirus 71 (EV71) is associated with severe neurological disorders in children, and has been implicated as the infectious agent in several large-scale outbreaks with mortalities. Upon infection, the viral RNA is translated in a cap-independent manner to yield a large polyprotein precursor. This mechanism relies on the presence of an internal ribosome entry site (IRES) element within the 5′-untranslated region. Virus-host interactions in EV71-infected cells are crucial in assisting this process. We identified a novel positive IRES trans-acting factor, far upstream element binding protein 1 (FBP1). Using binding assays, we mapped the RNA determinants within the EV71 IRES responsible for FBP1 binding and mapped the protein domains involved in this interaction. We also demonstrated that during EV71 infection, the nuclear protein FBP1 is enriched in cytoplasm where viral replication occurs. Moreover, we showed that FBP1 acts as a positive regulator of EV71 replication by competing with negative ITAF for EV71 IRES binding. These new findings may provide a route to new anti-viral therapy.

UR - http://www.scopus.com/inward/record.url?scp=83755205412&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=83755205412&partnerID=8YFLogxK

U2 - 10.1093/nar/gkr682

DO - 10.1093/nar/gkr682

M3 - Article

VL - 39

SP - 9633

EP - 9648

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 22

ER -