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J Virol, May 1998, p. 3684-3690, Vol. 72, No. 5
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Hepatitis Delta Antigen Mediates the Nuclear Import of Hepatitis Delta Virus RNA

Huei-Chi Chou,1 Tsai-Yuan Hsieh,1 Gwo-Tarng Sheu,1 and Michael M. C. Lai1,2,*

Department of Molecular Microbiology and Immunology1 and Howard Hughes Medical Institute,2 University of Southern California School of Medicine, Los Angeles, California 90033-1054

Received 10 December 1997/Accepted 29 January 1998

Hepatitis delta virus (HDV) RNA replicates in the nuclei of virus-infected cells. The mechanism of nuclear import of HDV RNA is so far unknown. Using a fluorescein-labeled HDV RNA introduced into partially permeabilized HeLa cells, we found that HDV RNA accumulated only in the cytoplasm. However, in the presence of hepatitis delta antigen (HDAg), which is the only protein encoded by HDV RNA, the HDV RNA was translocated into the nucleus, suggesting that nuclear import of HDV RNA is mediated by HDAg. Deletion of the nuclear localization signal (NLS) or RNA-binding motifs of HDAg resulted in the failure of nuclear import of HDV RNA, indicating that both the NLS and an RNA-binding motif of HDAg are required for the RNA-transporting activity of HDAg. Surprisingly, any one of the three previously identified RNA-binding motifs was sufficient to confer the RNA-transporting activity. We have further shown that HDAg, via its NLS, interacts with karyopherin alpha 2 in vitro, suggesting that nuclear import of the HDAg-HDV RNA complex is mediated by the karyopherin alpha 2beta heterodimer. The nuclear import of HDV RNA may be the first biological function of HDAg in the HDV life cycle.

* Corresponding author. Mailing address: Department of Molecular Microbiology and Immunology, University of Southern California School of Medicine, 2011 Zonal Ave., HMR-401, Los Angeles, CA 90033-1054. Phone: (213) 342-1748. Fax: (213) 342-9555. E-mail: Michlai{at}hsc.usc.edu.

J Virol, May 1998, p. 3684-3690, Vol. 72, No. 5
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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