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Science 23 April 1999:
Vol. 284. no. 5414, pp. 641 - 644
DOI: 10.1126/science.284.5414.641
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Reports

Efficient Persistence of Extrachromosomal KSHV DNA Mediated by Latency-Associated Nuclear Antigen

Mary E. Ballestas, 1 Pamela A. Chatis, 23 Kenneth M. Kaye 1*

Primary effusion lymphoma (PEL) cells harbor Kaposi's sarcoma-associated herpesvirus (KSHV) episomes and express a KSHV-encoded latency-associated nuclear antigen (LANA). In PEL cells, LANA and KSHV DNA colocalized in dots in interphase nuclei and along mitotic chromosomes. In the absence of KSHV DNA, LANA was diffusely distributed in the nucleus or on mitotic chromosomes. In lymphoblasts, LANA was necessary and sufficient for the persistence of episomes containing a specific KSHV DNA fragment. Furthermore, LANA colocalized with the artificial KSHV DNA episomes in nuclei and along mitotic chromosomes. These results support a model in which LANA tethers KSHV DNA to chromosomes during mitosis to enable the efficient segregation of KSHV episomes to progeny cells.

1 Department of Medicine, Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA.
2 Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
3 NEN Life Science Products, 549 Albany Street, Boston, MA 02118, USA.
*   To whom correspondence should be addressed. E-mail: kkaye{at}rics.bwh.harvard.edu

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   Abstract »    Full Text »    PDF »
Inhibition of Infection and Replication of Human Herpesvirus 8 in Microvascular Endothelial Cells by Alpha Interferon and Phosphonoformic Acid.
L. T. Krug, V. P. Pozharskaya, Y. Yu, N. Inoue, and M. K. Offermann (2004)
J. Virol. 78, 8359-8371
   Abstract »    Full Text »    PDF »
Accumulation of Heterochromatin Components on the Terminal Repeat Sequence of Kaposi's Sarcoma-Associated Herpesvirus Mediated by the Latency-Associated Nuclear Antigen.
S. Sakakibara, K. Ueda, K. Nishimura, E. Do, E. Ohsaki, T. Okuno, and K. Yamanishi (2004)
J. Virol. 78, 7299-7310
   Abstract »    Full Text »    PDF »
Mitotic Chromosome-Binding Activity of Latency-Associated Nuclear Antigen 1 Is Required for DNA Replication from Terminal Repeat Sequence of Kaposi's Sarcoma-Associated Herpesvirus.
C. Lim, C. Choi, and J. Choe (2004)
J. Virol. 78, 7248-7256
   Abstract »    Full Text »    PDF »
Kaposi's Sarcoma-Associated Herpesvirus-Encoded Latency-Associated Nuclear Antigen Inhibits Lytic Replication by Targeting Rta: a Potential Mechanism for Virus-Mediated Control of Latency.
K. Lan, D. A. Kuppers, S. C. Verma, and E. S. Robertson (2004)
J. Virol. 78, 6585-6594
   Abstract »    Full Text »    PDF »
Kaposi's Sarcoma-Associated Herpesvirus Induction of Chromosome Instability in Primary Human Endothelial Cells.
H. Pan, F. Zhou, and S.-J. Gao (2004)
Cancer Res. 64, 4064-4068
   Abstract »    Full Text »    PDF »
A naturally occurring C-terminal truncated isoform of the latent nuclear antigen of Kaposi's sarcoma-associated herpesvirus does not associate with viral episomal DNA.
M. Canham and S. J. Talbot (2004)
J. Gen. Virol. 85, 1363-1369
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Regulation and Autoregulation of the Promoter for the Latency-associated Nuclear Antigen of Kaposi's Sarcoma-associated Herpesvirus.
J. H. Jeong, J. Orvis, J. W. Kim, C. P. McMurtrey, R. Renne, and D. P. Dittmer (2004)
J. Biol. Chem. 279, 16822-16831
   Abstract »    Full Text »    PDF »
Identification of a virus trans-acting regulatory element on the latent DNA replication of Kaposi's sarcoma-associated herpesvirus.
C. Lim, T. Seo, J. Jung, and J. Choe (2004)
J. Gen. Virol. 85, 843-855
   Abstract »    Full Text »    PDF »
Vaccine potential of a murine gammaherpesvirus-68 mutant deficient for ORF73.
P. Fowler and S. Efstathiou (2004)
J. Gen. Virol. 85, 609-613
   Abstract »    Full Text »    PDF »
Analysis of Chromatin Attachment and Partitioning Functions of Bovine Papillomavirus Type 1 E2 Protein.
A. Abroi, I. Ilves, S. Kivi, and M. Ustav (2004)
J. Virol. 78, 2100-2113
   Abstract »    Full Text »    PDF »
The Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen 1 N Terminus Is Essential for Chromosome Association, DNA Replication, and Episome Persistence.
A. J. Barbera, M. E. Ballestas, and K. M. Kaye (2004)
J. Virol. 78, 294-301
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The herpesvirus saimiri ORF73 gene product interacts with host-cell mitotic chromosomes and self-associates via its C terminus.
M. A. Calderwood, K. T. Hall, D. A. Matthews, and A. Whitehouse (2004)
J. Gen. Virol. 85, 147-153
   Abstract »    Full Text »    PDF »
Transcriptional coactivation of c-Jun by the KSHV-encoded LANA.
J. An, Y. Sun, and M. B. Rettig (2004)
Blood 103, 222-228
   Abstract »    Full Text »    PDF »
Generation and precise modification of a herpesvirus saimiri bacterial artificial chromosome demonstrates that the terminal repeats are required for both virus production and episomal persistence.
R. E. White, M. A. Calderwood, and A. Whitehouse (2003)
J. Gen. Virol. 84, 3393-3403
   Abstract »    Full Text »    PDF »
ORF73 of murine herpesvirus-68 is critical for the establishment and maintenance of latency.
P. Fowler, S. Marques, J. P. Simas, and S. Efstathiou (2003)
J. Gen. Virol. 84, 3405-3416
   Abstract »    Full Text »    PDF »
ORF73 of Herpesvirus Saimiri Strain C488 Tethers the Viral Genome to Metaphase Chromosomes and Binds to cis-Acting DNA Sequences in the Terminal Repeats.
S. C. Verma and E. S. Robertson (2003)
J. Virol. 77, 12494-12506
   Abstract »    Full Text »    PDF »


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