PMID- 24367281
OWN - NLM
STAT- MEDLINE
DCOM- 20140820
LR  - 20211021
IS  - 1553-7404 (Electronic)
IS  - 1553-7390 (Print)
IS  - 1553-7390 (Linking)
VI  - 9
IP  - 12
DP  - 2013
TI  - Reactivation of chromosomally integrated human herpesvirus-6 by telomeric circle 
      formation.
PG  - e1004033
LID - 10.1371/journal.pgen.1004033 [doi]
LID - e1004033
AB  - More than 95% of the human population is infected with human herpesvirus-6 
      (HHV-6) during early childhood and maintains latent HHV-6 genomes either in an 
      extra-chromosomal form or as a chromosomally integrated HHV-6 (ciHHV-6). In 
      addition, approximately 1% of humans are born with an inheritable form of ciHHV-6 
      integrated into the telomeres of chromosomes. Immunosuppression and stress 
      conditions can reactivate latent HHV-6 replication, which is associated with 
      clinical complications and even death. We have previously shown that Chlamydia 
      trachomatis infection reactivates ciHHV-6 and induces the formation of 
      extra-chromosomal viral DNA in ciHHV-6 cells. Here, we propose a model and 
      provide experimental evidence for the mechanism of ciHHV-6 reactivation. 
      Infection with Chlamydia induced a transient shortening of telomeric ends, which 
      subsequently led to increased telomeric circle (t-circle) formation and 
      incomplete reconstitution of circular viral genomes containing single viral 
      direct repeat (DR). Correspondingly, short t-circles containing parts of the 
      HHV-6 DR were detected in cells from individuals with genetically inherited 
      ciHHV-6. Furthermore, telomere shortening induced in the absence of Chlamydia 
      infection also caused circularization of ciHHV-6, supporting a t-circle based 
      mechanism for ciHHV-6 reactivation.
FAU - Prusty, Bhupesh K
AU  - Prusty BK
AD  - Chair of Microbiology, Biocenter, University of Wurzburg, Wurzburg, Germany.
FAU - Krohne, George
AU  - Krohne G
AD  - Electron Microscopy Core Facility, Biocenter, University of Wurzburg, Wurzburg, 
      Germany.
FAU - Rudel, Thomas
AU  - Rudel T
AD  - Chair of Microbiology, Biocenter, University of Wurzburg, Wurzburg, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131219
PL  - United States
TA  - PLoS Genet
JT  - PLoS genetics
JID - 101239074
RN  - 0 (DNA, Viral)
SB  - IM
MH  - Chlamydia trachomatis/pathogenicity/virology
MH  - Chlamydiaceae Infections/genetics/pathology/virology
MH  - Chromosomes, Human/*genetics
MH  - DNA, Viral/*genetics
MH  - Genome, Viral
MH  - Herpesvirus 6, Human/*genetics
MH  - Humans
MH  - Telomere/*genetics
MH  - Telomere Shortening/genetics
MH  - Virus Integration/genetics
MH  - Virus Latency/genetics
MH  - Virus Replication/genetics
PMC - PMC3868596
COIS- The authors have declared that no competing interests exist.
EDAT- 2013/12/25 06:00
MHDA- 2014/08/21 06:00
PMCR- 2013/12/01
CRDT- 2013/12/25 06:00
PHST- 2013/09/10 00:00 [received]
PHST- 2013/11/01 00:00 [accepted]
PHST- 2013/12/25 06:00 [entrez]
PHST- 2013/12/25 06:00 [pubmed]
PHST- 2014/08/21 06:00 [medline]
PHST- 2013/12/01 00:00 [pmc-release]
AID - PGENETICS-D-13-02437 [pii]
AID - 10.1371/journal.pgen.1004033 [doi]
PST - ppublish
SO  - PLoS Genet. 2013;9(12):e1004033. doi: 10.1371/journal.pgen.1004033. Epub 2013 Dec 
      19.