PMID- 9420230
OWN - NLM
STAT- MEDLINE
DCOM- 19980128
LR  - 20200724
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 72
IP  - 1
DP  - 1998 Jan
TI  - Functional identification and analysis of cis-acting sequences which mediate 
      genome cleavage and packaging in human herpesvirus 6.
PG  - 320-9
AB  - Sequences present at the genomic termini of herpesviruses become linked during 
      lytic-phase replication and provide the substrate for cleavage and packaging of 
      unit length viral genomes. We have previously shown that homologs of the 
      consensus herpesvirus cleavage-packaging signals, pac1 and pac2, are located at 
      the left and right genomic termini of human herpesvirus 6 (HHV-6), respectively. 
      Immediately adjacent to these elements are two distinct arrays of human telomeric 
      repeat sequences (TRS). We now show that the unique sequence element formed at 
      the junction of HHV-6B genome concatemers (pac2-pac1) is necessary and sufficient 
      for virally mediated cleavage of plasmid DNAs containing the HHV-6B lytic-phase 
      origin of DNA replication (oriLyt). The concatemeric junction sequence also 
      allowed for the packaging of these plasmid molecules into intracellular 
      nucleocapsids as well as mature, infectious viral particles. In addition, this 
      element significantly enhanced the replication efficiency of oriLyt-containing 
      plasmids in virally infected cells. Experiments revealed that the concatemeric 
      junction sequence possesses an unusual, S1 nuclease-sensitive conformation 
      (anisomorphic DNA), which might play a role in this apparent enhancement of DNA 
      replication--although additional studies will be required to test this 
      hypothesis. Finally, we also analyzed whether the presence of flanking viral TRS 
      had any effect on the functional activity of the minimal concatemeric junction 
      (pac2-pac1). These experiments revealed that the TRS motifs, either alone or in 
      combination, had no effect on the efficiency of virally mediated DNA replication 
      or DNA cleavage. Taken together, these data show that the cleavage and packaging 
      of HHV-6 DNA are mediated by cis-acting consensus sequences similar to those 
      found in other herpesviruses, and that these sequences also influence the 
      efficiency of HHV-6 DNA replication. Since the adjacent TRS do not influence 
      either viral cleavage and packaging or viral DNA replication, their function 
      remains uncertain.
FAU - Deng, H
AU  - Deng H
AD  - Department of Microbiology and Immunology, University of Rochester Medical 
      Center, New York 14642, USA.
FAU - Dewhurst, S
AU  - Dewhurst S
LA  - eng
GR  - KO4 AI01240/AI/NIAID NIH HHS/United States
GR  - R01 AI34231/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (DNA Primers)
SB  - IM
MH  - Base Sequence
MH  - Cell Line
MH  - DNA Primers/genetics
MH  - DNA Replication/genetics/physiology
MH  - *Genome, Viral
MH  - Herpesvirus 6, Human/*genetics/*growth & development/physiology
MH  - Humans
MH  - Molecular Sequence Data
MH  - Plasmids/genetics
MH  - Polymerase Chain Reaction
MH  - Repetitive Sequences, Nucleic Acid
MH  - Signal Transduction
MH  - Telomere/genetics
MH  - Virus Replication/genetics/physiology
PMC - PMC109379
EDAT- 1998/01/07 00:00
MHDA- 1998/01/07 00:01
PMCR- 1998/01/01
CRDT- 1998/01/07 00:00
PHST- 1998/01/07 00:00 [pubmed]
PHST- 1998/01/07 00:01 [medline]
PHST- 1998/01/07 00:00 [entrez]
PHST- 1998/01/01 00:00 [pmc-release]
AID - 1094 [pii]
AID - 10.1128/JVI.72.1.320-329.1998 [doi]
PST - ppublish
SO  - J Virol. 1998 Jan;72(1):320-9. doi: 10.1128/JVI.72.1.320-329.1998.