Kaposi's sarcoma-associated herpesvirus-encoded LANA can interact with the nuclear mitotic apparatus protein to regulate genome maintenance and segregation.
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.
Si
Huaxin
H
Department of Microbiology and the Abramson Comprehensive Cancer Center, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Verma
Subhash C
SC
Lampson
Michael A
MA
Cai
Qiliang
Q
Robertson
Erle S
ES
D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism*; D000956:Antigens, Viral / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D018797:Cell Cycle Proteins; D002460:Cell Line; D020090:Chromosome Segregation / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D016679:Genome, Viral / Q000235:genetics*; D019288:Herpesvirus 8, Human / Q000235:genetics*; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000378:metabolism; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D034622:RNA Interference
D034961:Antigens, Nuclear; D000956:Antigens, Viral; D018797:Cell Cycle Proteins; D017931:DNA Primers; C050045:NUMA1 protein, human; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins; C109540:latency-associated nuclear antigen