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Journal of Virology, July 2008, p. 6734-6746, Vol. 82, No. 13
0022-538X/08/$08.00+0     doi:10.1128/JVI.00342-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Kaposi's Sarcoma-Associated Herpesvirus-Encoded LANA Can Interact with the Nuclear Mitotic Apparatus Protein To Regulate Genome Maintenance and Segregation{triangledown} ,{dagger}

Huaxin Si,1 Subhash C. Verma,1 Michael A. Lampson,2 Qiliang Cai,1 and Erle S. Robertson1*

Department of Microbiology and the Tumor Virology Program of the Abramson Comprehensive Cancer Center, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104,1 Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 191042

Received 16 February 2008/ Accepted 9 April 2008

Kaposi's sarcoma-associated herpesvirus (KSHV) genomes are tethered to the host chromosomes and partitioned faithfully into daughter cells with the host chromosomes. The latency-associated nuclear antigen (LANA) is important for segregation of the newly synthesized viral genomes to the daughter nuclei. Here, we report that the nuclear mitotic apparatus protein (NuMA) and LANA can associate in KSHV-infected cells. In synchronized cells, NuMA and LANA are colocalized in interphase cells and separate during mitosis at the beginning of prophase, reassociating again at the end of telophase and cytokinesis. Silencing of NuMA expression by small interfering RNA and expression of LGN and a dominant-negative of dynactin (P150-CC1), which disrupts the association of NuMA with microtubules, resulted in the loss of KSHV terminal-repeat plasmids containing the major latent origin. Thus, NuMA is required for persistence of the KSHV episomes in daughter cells. This interaction between NuMA and LANA is critical for segregation and maintenance of the KSHV episomes through a temporally controlled mechanism of binding and release during specific phases of mitosis.


* Corresponding author. Mailing address: Department of Microbiology and the Abramson Comprehensive Cancer Center, School of Medicine, University of Pennsylvania, 202E Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104. Phone: (215) 746-0114. Fax: (215) 898-9557. E-mail: erle{at}mail.med.upenn.edu

{triangledown} Published ahead of print on 16 April 2008.

{dagger} Supplemental material for this article can be found at http://jvi.asm.org/.


Journal of Virology, July 2008, p. 6734-6746, Vol. 82, No. 13
0022-538X/08/$08.00+0     doi:10.1128/JVI.00342-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

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