JVI Accepts, published online ahead of print on 16 April 2008

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J. Virol. doi:10.1128/JVI.00342-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

KSHV Encoded LANA can Interact with the Nuclear Mitotic Apparatus Protein to Regulate Genome Maintenance and Segregation

Huaxin Si, Subhash C. Verma, Michael Lampson, Qiliang Cai, and Erle S. Robertson^*

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

^* To whom correspondence should be addressed. Email: erle{at}mail.med.upenn.edu.

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 telophase and cytokinesis. Silencing of NuMA expression by siRNA and expression of LGN and a dominant negative of dynactin (P150-CC1) which disrupts the association of NuMA with microtubule resulted in the loss of KSHV terminal repeats plasmids containing the major latent origin. Thus, NuMA is required for persistence of the KSHV episomes to 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.

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