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Journal of Virology, June 2000, p. 5329-5336, Vol. 74, No. 11
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Hepatitis Delta Virus Replication Generates
Complexes of Large Hepatitis Delta Antigen and Antigenomic RNA That
Affiliate with and Alter Nuclear Domain 10
Peter
Bell,1
Robert
Brazas,2
Donald
Ganem,2 and
Gerd G.
Maul1,*
The Wistar Institute, Philadelphia,
Pennsylvania 19104,1 and Howard Hughes
Medical Institute and Departments of Microbiology and Medicine,
University of California, San Francisco, California
941432
Received 2 December 1999/Accepted 22 February 2000
Hepatitis delta virus (HDV), a single-stranded RNA virus, bears a
single coding region whose product, the hepatitis delta antigen (HDAg),
is expressed in two isoforms, small (S-HDAg) and large (L-HDAg). S-HDAg
is required for replication of HDV, while L-HDAg inhibits viral
replication and is required for the envelopment of the HDV genomic RNA
by hepatitis B virus proteins. Here we have examined the spatial
distribution of HDV RNA and proteins in infected nuclei, with
particular reference to specific nuclear domains. We found that L-HDAg
was aggregated in specific nuclear domains and that over half of these
domains were localized beside nuclear domain 10 (ND10). At later times,
ND10-associated proteins like PML were found in larger HDAg complexes
that had developed into apparently hollow spheres. In these larger
complexes, PML was found chiefly in the rims of the spheres, while the
known ND10 components Sp100, Daxx, and NDP55 were found in the centers of the spheres. Thus, ND10 proteins that normally are closely linked
separate within HDAg-associated complexes. Viral RNA of antigenomic
polarity, whether expressed from genomic RNA or directly from
introduced plasmids, colocalizes with L-HDAg and the transcriptional repressor PML. In contrast, HDV genomic RNA was distributed more uniformly throughout the nucleus. These results suggest that different host protein complexes may assemble on viral RNA strands of different polarities, and they also suggest that this RNA virus, like DNA viruses, can alter the distribution of ND10-associated proteins. The
fact that viral components specifically linked to repression of
replication can associate with one of the ND10-associated proteins (PML) raises the possibility that this host protein may play a role in
the regulation of HDV RNA synthesis.
*
Corresponding author. Mailing address: The Wistar
Institute, 3601 Spruce St., Philadelphia, PA 19104. Phone: (215)
898-3817. Fax: (215) 898-3868. E-mail:
maul{at}wistar.upenn.edu.
Journal of Virology, June 2000, p. 5329-5336, Vol. 74, No. 11
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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