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Journal of Virology, June 2009, p. 6106-6114, Vol. 83, No. 12
0022-538X/09/$08.00+0     doi:10.1128/JVI.02476-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

hnRNP A1 Interacts with the 5' Untranslated Regions of Enterovirus 71 and Sindbis Virus RNA and Is Required for Viral Replication{triangledown}

Jing-Yi Lin,1,3 Shin-Ru Shih,1,2,3 Manjing Pan,4 Carol Li,4 Chia-Fang Lue,4 Victor Stollar,4,5 and Mei-Ling Li4*

Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Tao-Yuan, Taiwan,1 Clinical Virology Laboratory, Department of Clinical Pathology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan,2 Research Center for Emerging Viral Infections, Chang Gung University, Tao-Yuan, Taiwan,3 Department of Molecular Genetics, Microbiology, and Immunology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854,4 Cancer Institute of New Jersey, New Brunswick, New Jersey 089035

Received 2 December 2008/ Accepted 23 March 2009

Heterogeneous nuclear ribonucleoprotein (hnRNP) A1 is involved in pre-mRNA splicing in the nucleus and translational regulation in the cytoplasm. The cytoplasmic redistribution of hnRNP A1 is a regulated process during viral infection and cellular stress. Here we demonstrate that hnRNP A1 not only is an internal ribosome entry site (IRES) trans-acting factor that binds specifically to the 5' untranslated region (UTR) of enterovirus 71 (EV71) and regulates IRES-dependent translation but also binds to the 5' UTR of Sindbis virus (SV) and facilitates its translation. The cytoplasmic relocalization of hnRNP A1 in EV71-infected cells leads to the enhancement of EV71 IRES-mediated translation, and its function can be substituted by hnRNP A2, whereas the cytoplasmic relocalization of hnRNP A1 following SV infection enhances the SV translation, but this function cannot be replaced by hnRNP A2. Our study provides the first direct evidence that the cytoplasmic relocalization of hnRNP A1 controls not only the IRES-dependent but also non-IRES-dependent translation initiations of RNA viruses.


* Corresponding author. Mailing address: Department of Molecular Genetics, Microbiology, and Immunology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854. Phone: (732) 235-5449. Fax: (732) 235-5223. E-mail: lime{at}umdnj.edu

{triangledown} Published ahead of print on 1 April 2009.


Journal of Virology, June 2009, p. 6106-6114, Vol. 83, No. 12
0022-538X/09/$08.00+0     doi:10.1128/JVI.02476-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.