PMID- 21593154
OWN - NLM
STAT- MEDLINE
DCOM- 20110921
LR  - 20211020
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 85
IP  - 15
DP  - 2011 Aug
TI  - Epithelial cell retention of transcriptionally active, P3HR-1-derived 
      heterogeneous Epstein-Barr virus DNA with concurrent loss of parental virus.
PG  - 7634-43
LID - 10.1128/JVI.00045-11 [doi]
AB  - Deleted, rearranged, heterogeneous (het) Epstein-Barr virus (EBV) DNA with the 
      distinctive capability of disrupting EBV latency has been reported in biopsy 
      samples of EBV-associated tumors whose onset in immunocompetent hosts is 
      characteristically preceded by an antibody response indicative of EBV 
      reactivation. Using the EBV P3HR-1 strain, we have reproduced in long-term 
      culture of SVK epithelial cells an unusual pattern of infection previously 
      observed in a subset of tumor biopsy samples: the persistence of het DNA in the 
      absence of the parental helper virus. Fluorescence in situ hybridization (FISH) 
      of infected cell subclones indicated the retention of het DNA in an integrated 
      form. Incorporation of an intact het DNA molecule was confirmed by PCR, using 
      primers that framed junctions of the four rearranged EBV DNA segments comprising 
      P3HR-1-derived het DNA. Structural analysis of EBV terminal repeats revealed a 
      banding pattern consistent with the integration of het DNA as a concatemer. 
      Linkage of concatemeric monomers was defined at a nucleotide level, and that 
      junctional sequence was detected in cell-free P3HR-1 virion DNA, confirming that 
      subgenomic het DNA was packaged into infectious particles in a concatemeric 
      configuration. Stable integration into cells having lost the standard viral 
      genome allowed the unambiguous designation of het DNA as the source for viral 
      gene products potentially encoded by both. Continuous expression of the 
      latency-to-lytic switch protein Zta and detection of the BALF4 gene product gB, 
      known to expand the target cell range of standard virus when incorporated at 
      augmented levels into infectious progeny, add to a presumption of het 
      DNA-enhanced pathogenesis in diseases of EBV reactivation.
FAU - Ikuta, Kazufumi
AU  - Ikuta K
AD  - Center for Molecular and Tumor Virology, LSU Health Sciences Center, 1501 Kings 
      Highway, Shreveport, LA 71130, USA.
FAU - Ding, Mingyu
AU  - Ding M
FAU - Zhang, Fangfang
AU  - Zhang F
FAU - Sixbey, John W
AU  - Sixbey JW
FAU - Scott, Rona S
AU  - Scott RS
LA  - eng
GR  - R01 CA114416/CA/NCI NIH HHS/United States
GR  - P20 RR018724/RR/NCRR NIH HHS/United States
GR  - R01 CA067372/CA/NCI NIH HHS/United States
GR  - CA114416/CA/NCI NIH HHS/United States
GR  - CA67372/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110518
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Antibodies, Viral)
RN  - 0 (DNA Primers)
RN  - 0 (DNA, Viral)
SB  - IM
MH  - Antibodies, Viral/biosynthesis
MH  - Base Sequence
MH  - Blotting, Southern
MH  - Cell Line, Tumor
MH  - DNA Primers
MH  - DNA, Viral/*genetics
MH  - Epithelial Cells/*virology
MH  - Genome, Viral
MH  - Herpesvirus 4, Human/*genetics/immunology/physiology
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - *Transcription, Genetic
MH  - Virus Integration
PMC - PMC3147926
EDAT- 2011/05/20 06:00
MHDA- 2011/09/22 06:00
PMCR- 2012/02/01
CRDT- 2011/05/20 06:00
PHST- 2011/05/20 06:00 [entrez]
PHST- 2011/05/20 06:00 [pubmed]
PHST- 2011/09/22 06:00 [medline]
PHST- 2012/02/01 00:00 [pmc-release]
AID - JVI.00045-11 [pii]
AID - 0045-11 [pii]
AID - 10.1128/JVI.00045-11 [doi]
PST - ppublish
SO  - J Virol. 2011 Aug;85(15):7634-43. doi: 10.1128/JVI.00045-11. Epub 2011 May 18.