Kaposi’s sarcoma–associated herpesvirus stably clusters its genomes across generations to maintain itself extrachromosomally

Chiu, Ya-Fang; Sugden, Arthur U.; Fox, Kathryn; Hayes, Mitchell; Sugden, Bill

doi:10.1083/jcb.201702013

Kaposi’s sarcoma–associated herpesvirus stably clusters its genomes across generations to maintain itself extrachromosomally

Journal Article · Mon Jul 10 00:00:00 UTC 2017 · Journal of Cell Biology

DOI:https://doi.org/10.1083/jcb.201702013· OSTI ID:1368608

Chiu, Ya-Fang; Sugden, Arthur U.; ; ;

Genetic elements that replicate extrachromosomally are rare in mammals; however, several human tumor viruses, including the papillomaviruses and the gammaherpesviruses, maintain their plasmid genomes by tethering them to cellular chromosomes. We have uncovered an unprecedented mechanism of viral replication: Kaposi’s sarcoma–associated herpesvirus (KSHV) stably clusters its genomes across generations to maintain itself extrachromosomally. To identify and characterize this mechanism, we developed two complementary, independent approaches: live-cell imaging and a predictive computational model. The clustering of KSHV requires the viral protein, LANA1, to bind viral genomes to nucleosomes arrayed on both cellular and viral DNA. Clustering affects both viral partitioning and viral genome numbers of KSHV. The clustering of KSHV plasmids provides it with an effective evolutionary strategy to rapidly increase copy numbers of genomes per cell at the expense of the total numbers of cells infected.

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Research Organization:: Univ. of Wisconsin, Madison, WI (United States)

Sponsoring Organization:: Chang Gung Memorial Hospital, Linkou; Ministry of Science and Technology, Taiwan; National Cancer Institute (NCI); National Health Research Institute; National Science Foundation (NSF); USDOE; USDOE Office of Science (SC)

Other Award/Contract Number:: P01 CA022443
R01 CA133027
R01 CA070723
MOST-105-2320-B-182-033
NHRI-EX106-10623BI
P30 CA014520
BMRPF14

OSTI ID:: 1368608

Alternate ID(s):: OSTI ID: 1904058

Journal Information:: Journal of Cell Biology, Journal Name: Journal of Cell Biology Journal Issue: 9 Vol. 216; ISSN 0021-9525

Publisher:: Rockefeller University PressCopyright Statement

Country of Publication:: United States

Language:: English

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