The latency-associated nuclear antigen tethers the Kaposi's sarcoma-associated herpesvirus genome to host chromosomes in body cavity-based lymphoma cells.
Viruses that establish latent infection must maintain their DNA in the host nucleus through many cellular generations. Here we identify a novel mechanism by which the gammaherpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) may achieve this persistence in latently infected body cavity-based lymphoma (BCBL) cells. We find that KSHV genomic DNA is associated with host chromosomes and colocalizes with the latency-associated nuclear antigen (LANA). Furthermore, a region at the left end of the KSHV genome binds strongly to LANA and can colocalize to the host chromosomes with LANA. Additionally, we found that LANA associates with histone H1 in KSHV-infected BCBL cells. We propose that this chromosomal association of the KSHV genome is mediated by LANA and involves a tethering mechanism by which viral episomes are linked to host chromatin through simultaneous interaction with host chromosomal proteins including histone H1 and cis-acting KSHV DNA elements. This strategy may be employed by other viruses in establishment of latency in the infected cells.
Cotter
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Department of Microbiology, University of Michigan Medical Center, 1150 West Medical Center Drive, 6723 MS II, Ann Arbor, Michigan, 48109, USA.
Robertson
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D000956:Antigens, Viral / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D004279:DNA, Viral / Q000378:metabolism; D016679:Genome, Viral; D019288:Herpesvirus 8, Human / Q000235:genetics* / Q000502:physiology; D006657:Histones / Q000378:metabolism; D006801:Humans; D008223:Lymphoma; D008677:Metaphase; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009707:Nucleosomes; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012514:Sarcoma, Kaposi / Q000821:virology*; D014407:Tumor Cells, Cultured; D016662:Virus Integration; D017735:Virus Latency
D000956:Antigens, Viral; D004279:DNA, Viral; D006657:Histones; D009687:Nuclear Proteins; D009707:Nucleosomes; D011993:Recombinant Fusion Proteins; C109540:latency-associated nuclear antigen