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.
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
2 in vitro, suggesting that nuclear
import of the HDAg-HDV RNA complex is mediated by the karyopherin
2
heterodimer. The nuclear import of HDV RNA may be the first
biological function of HDAg in the HDV life cycle.
This article has been cited by other articles:
| J. Bacteriol. | Mol. Cell. Biol. | Microbiol. Mol. Biol. Rev. |
|---|
| Clin. Vaccine Immunol. | ALL ASM JOURNALS |
|---|