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J. Biol. Chem., Vol. 282, Issue 42, 30497-30508, October 19, 2007

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Y Box-binding Protein-1 Binds to the Dengue Virus 3'-Untranslated Region and Mediates Antiviral Effects^*

From the Division of Infectious Diseases, School of Public Health, University of California, Berkeley, California 94720-7360

Dengue virus, a member of the family Flaviviridae, poses a serious public health threat worldwide. Dengue virus is a positive-sense RNA virus that harbors a genome of 10.7 kb. Replication of dengue virus is mediated coordinately by cis-acting genomic sequences, viral proteins, and host cell factors. We have isolated and identified several host cell factors from baby hamster kidney cell extracts that bind with high specificity and high affinity to sequences within the untranslated regions of the dengue virus genome. Among the factors identified, Y box-binding protein-1 (YB-1) and the heterogeneous nuclear ribonucleoproteins (hnRNPs), hnRNP A1, hnRNP A2/B1, and hnRNP Q, bind to the dengue virus 3'-untranslated region. Further analysis indicated that YB-1 binds to the dengue virus 3' stem loop, a conserved structural feature located at the 3' terminus of the 3'-untranslated region of many flaviviruses. Analysis of the impact of YB-1 on replication of dengue virus in YB-1^+/+ and YB-1^–/– mouse embryo fibroblasts indicated that host YB-1 mediates an antiviral effect. Further studies demonstrated that this antiviral impact is due, at least in part, to a repressive role of YB-1 on dengue virus translation via a mechanism that requires viral genomic sequences. These results suggest a novel role for YB-1 as an antiviral host cell factor.

Received for publication, July 13, 2007 , and in revised form, August 28, 2007.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Division of Infectious Diseases, School of Public Health, University of California, Berkeley, 50 University Hall, Berkeley, CA 94720-7360. Tel.: 510-642-4845; Fax: 510-642-6350; E-mail: eharris{at}berkeley.edu.

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