PMID- 20660191
OWN - NLM
STAT- MEDLINE
DCOM- 20100928
LR  - 20211203
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 84
IP  - 19
DP  - 2010 Oct
TI  - Bub1 and CENP-F can contribute to Kaposi's sarcoma-associated herpesvirus genome 
      persistence by targeting LANA to kinetochores.
PG  - 9718-32
LID - 10.1128/JVI.00713-10 [doi]
AB  - The latency-associated nuclear antigen (LANA) encoded by Kaposi's 
      sarcoma-associated herpesvirus (KSHV) is critical for segregation of viral 
      episomes to progeny nuclei and allows for maintenance of the viral genome in 
      newly divided daughter cells. LANA binds to KSHV terminal repeat (TR) DNA and 
      simultaneously associates with chromatin-bound cellular proteins. This process 
      tethers the viral episomes to host chromosomes. However, the mechanism of 
      tethering is complex and involves multiple protein-protein interactions. Our 
      previous proteomics studies which showed the association of LANA with centromeric 
      protein F (CENP-F) prompted us to further study whether LANA targets centromeric 
      proteins for persistence of KSHV episomes during cell division. Here we show that 
      LANA colocalized with CENP-F as speckles, some of which are paired at centromeric 
      regions of a subset of chromosomes in KSHV-infected JSC-1 cells. We also confirm 
      that both the amino and carboxy termini of LANA can bind to CENP-F. Moreover, 
      LANA associated with another kinetochore protein, Bub1 (budding uninhibited by 
      benzimidazole 1), which is known to form a complex with CENP-F. Importantly, we 
      demonstrated the dynamic association of LANA and Bub1/CENP-F and the 
      colocalization between Bub1, LANA, and the KSHV episome tethered to the host 
      chromosome using fluorescence in situ hybridization (FISH). Knockdown of Bub1 
      expression by lentivirus-delivered short hairpin RNA (shRNA) dramatically reduced 
      the number of KSHV genome copies, whereas no dramatic effect was seen with CENP-F 
      knockdown. Therefore, the interaction between LANA and the kinetochore proteins 
      CENP-F and Bub1 is important for KSHV genome tethering and its segregation to new 
      daughter cells, with Bub1 potentially playing a more critical role in the 
      long-term persistence of the viral genome in the infected cell.
FAU - Xiao, Bingyi
AU  - Xiao B
AD  - Department of Microbiology and Tumor Virology Program of the Abramson 
      Comprehensive Cancer Center, University of Pennsylvania School of Medicine, 
      Philadelphia, PA 19104, USA.
FAU - Verma, Subhash C
AU  - Verma SC
FAU - Cai, Qiliang
AU  - Cai Q
FAU - Kaul, Rajeev
AU  - Kaul R
FAU - Lu, Jie
AU  - Lu J
FAU - Saha, Abhik
AU  - Saha A
FAU - Robertson, Erle S
AU  - Robertson ES
LA  - eng
GR  - R00 CA126182-03/CA/NCI NIH HHS/United States
GR  - R01 CA091792/CA/NCI NIH HHS/United States
GR  - CA137894/CA/NCI NIH HHS/United States
GR  - CA108461/CA/NCI NIH HHS/United States
GR  - CA138434/CA/NCI NIH HHS/United States
GR  - CA091792/CA/NCI NIH HHS/United States
GR  - K99 CA126182/CA/NCI NIH HHS/United States
GR  - AI067037/AI/NIAID NIH HHS/United States
GR  - CA115299/CA/NCI NIH HHS/United States
GR  - CA126182/CA/NCI NIH HHS/United States
GR  - R01 CA138434/CA/NCI NIH HHS/United States
GR  - R00 CA126182/CA/NCI NIH HHS/United States
GR  - R01 AI067037/AI/NIAID NIH HHS/United States
GR  - T32 CA115299/CA/NCI NIH HHS/United States
GR  - R00 CA126182-04/CA/NCI NIH HHS/United States
GR  - R01 CA108461/CA/NCI NIH HHS/United States
GR  - R01 CA137894/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100721
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Antigens, Viral)
RN  - 0 (Chromosomal Proteins, Non-Histone)
RN  - 0 (Microfilament Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (centromere protein F)
RN  - 0 (latency-associated nuclear antigen)
RN  - EC 2.7.11.1 (BUB1 protein, human)
RN  - EC 2.7.11.1 (Bub1 spindle checkpoint protein)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Antigens, Viral/chemistry/genetics/*metabolism
MH  - Base Sequence
MH  - Cell Line
MH  - Chromosomal Proteins, Non-Histone/antagonists & inhibitors/genetics/*metabolism
MH  - Gene Knockdown Techniques
MH  - Genome, Viral
MH  - Herpesvirus 8, Human/*genetics/pathogenicity/*physiology
MH  - Host-Pathogen Interactions
MH  - Humans
MH  - In Vitro Techniques
MH  - Kinetochores/metabolism/*virology
MH  - Microfilament Proteins/antagonists & inhibitors/genetics/*metabolism
MH  - Mitosis
MH  - Models, Biological
MH  - Nuclear Proteins/chemistry/genetics/*metabolism
MH  - Plasmids/genetics
MH  - Protein Interaction Mapping
MH  - Protein Serine-Threonine Kinases/antagonists & inhibitors/genetics/*metabolism
MH  - RNA, Small Interfering/genetics
PMC - PMC2937805
EDAT- 2010/07/28 06:00
MHDA- 2010/09/30 06:00
PMCR- 2011/04/01
CRDT- 2010/07/28 06:00
PHST- 2010/07/28 06:00 [entrez]
PHST- 2010/07/28 06:00 [pubmed]
PHST- 2010/09/30 06:00 [medline]
PHST- 2011/04/01 00:00 [pmc-release]
AID - JVI.00713-10 [pii]
AID - 0713-10 [pii]
AID - 10.1128/JVI.00713-10 [doi]
PST - ppublish
SO  - J Virol. 2010 Oct;84(19):9718-32. doi: 10.1128/JVI.00713-10. Epub 2010 Jul 21.