PMID- 15507596
OWN - NLM
STAT- MEDLINE
DCOM- 20041123
LR  - 20181113
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 78
IP  - 22
DP  - 2004 Nov
TI  - Construction of a herpes simplex virus type 1 mutant with only a three-nucleotide 
      change in the branchpoint region of the latency-associated transcript (LAT) and 
      the stability of its two-kilobase LAT intron.
PG  - 12097-106
AB  - Previous studies using a eukaryotic expression system indicated that the unusual 
      stability of the latency-associated transcript (LAT) intron was due to its 
      nonconsensus branchpoint sequence (T.-T Wu, Y.-H. Su, T. M. Block, and J. M. 
      Taylor, Virology, 243:140-149, 1998). The present study investigated the role of 
      the branchpoint sequence in the stability of the intron expressed from the herpes 
      simplex virus type 1 (HSV-1) genome and the role of LAT intron stability in the 
      HSV-1 life cycle. A branchpoint mutant called Sy2 and the corresponding rescued 
      viruses, SyRA and SyRB, were constructed. To preserve the coding sequence of the 
      immediate early gene icp0, which overlaps with the branchpoint region of the 2-kb 
      LAT, a 3-nucleotide mutation into the branchpoint region of the 2-kb LAT was 
      introduced, resulting in a branchpoint that is 85% identical to the consensus 
      intron branchpoint sequence of eukaryotic cells. As anticipated, there was a 90- 
      to 96-fold reduction in 2-kb LAT accumulation following productive infection in 
      tissue culture and latent infection in mice with Sy2, as determined by Northern 
      blot analysis. These results clearly suggest that the accumulation of the 2-kb 
      intron in tissue culture and in vivo is, at least in part, due to the 
      nonconsensus branchpoint sequence of the LAT intron. Interestingly, a failure to 
      accumulate LAT was associated with greater progeny production of Sy2 at a low 
      multiplicity of infection (0.01) in tissue culture, but not in mice. However, the 
      ability of mutant Sy2 to reactivate from trigeminal ganglia (TG) derived from 
      latently infected mice was indistinguishable from that of wild-type virus, as 
      assayed in the mouse TG explant reactivation system.
FAU - Ng, Alan K
AU  - Ng AK
AD  - Department of Biochemistry and Molecular Pharmacology, Jefferson Center for 
      Biomedical Research, Thomas Jefferson University, 700 E. Butler Avenue, 
      Doylestown, PA 18901-2697, USA.
FAU - Block, Timothy M
AU  - Block TM
FAU - Aiamkitsumrit, Benjamas
AU  - Aiamkitsumrit B
FAU - Wang, Mengjun
AU  - Wang M
FAU - Clementi, Emily
AU  - Clementi E
FAU - Wu, Ting-Ting
AU  - Wu TT
FAU - Taylor, John M
AU  - Taylor JM
FAU - Su, Ying-Hsiu
AU  - Su YH
LA  - eng
GR  - P01 NS033768/NS/NINDS NIH HHS/United States
GR  - P50 NS033768/NS/NINDS NIH HHS/United States
GR  - NS 33768-11/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (MicroRNAs)
RN  - 0 (Viral Proteins)
RN  - 0 (latency associated transcript, herpes simplex virus-1)
SB  - IM
MH  - Animals
MH  - Female
MH  - Herpesvirus 1, Human/*genetics/growth & development
MH  - *Introns
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - MicroRNAs
MH  - Mutation
MH  - Viral Proteins/*genetics
MH  - Virus Activation
PMC - PMC525071
EDAT- 2004/10/28 09:00
MHDA- 2004/12/16 09:00
PMCR- 2004/11/01
CRDT- 2004/10/28 09:00
PHST- 2004/10/28 09:00 [pubmed]
PHST- 2004/12/16 09:00 [medline]
PHST- 2004/10/28 09:00 [entrez]
PHST- 2004/11/01 00:00 [pmc-release]
AID - 78/22/12097 [pii]
AID - 0760-04 [pii]
AID - 10.1128/JVI.78.22.12097-12106.2004 [doi]
PST - ppublish
SO  - J Virol. 2004 Nov;78(22):12097-106. doi: 10.1128/JVI.78.22.12097-12106.2004.