PMID- 16352568
OWN - NLM
STAT- MEDLINE
DCOM- 20070126
LR  - 20191210
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 80
IP  - 1
DP  - 2006 Jan
TI  - Point mutations in herpes simplex virus type 1 oriL, but not in oriS, reduce 
      pathogenesis during acute infection of mice and impair reactivation from latency.
PG  - 440-50
AB  - In vitro studies of herpes simplex virus type 1 (HSV-1) viruses containing 
      mutations in core sequences of the viral origins of DNA replication, oriL and 
      oriS, that eliminate the ability of these origins to initiate viral-DNA synthesis 
      have demonstrated little or no effect on viral replication in cultured cells, 
      leading to the conclusion that the two types of origins are functionally 
      redundant. It remains unclear, therefore, why origins that appear to be redundant 
      are maintained evolutionarily in HSV-1 and other neurotropic alphaherpesviruses. 
      To test the hypothesis that oriL and oriS have distinct functions in the HSV-1 
      life cycle in vivo, we determined the in vivo phenotypes of two mutant viruses, 
      DoriL-I(LR) and DoriS-I, containing point mutations in oriL and oriS site I, 
      respectively, that eliminate origin DNA initiation function. Following corneal 
      inoculation of mice, tear film titers of DoriS-I were reduced relative to 
      wild-type virus. In all other tests, however, DoriS-I behaved like wild-type 
      virus. In contrast, titers of DoriL-I(LR) in tear film, trigeminal ganglia (TG), 
      and hindbrain were reduced and mice infected with DoriL-I(LR) exhibited greatly 
      reduced mortality relative to wild-type virus. In the TG explant and TG cell 
      culture models of reactivation, DoriL-I(LR) reactivated with delayed kinetics 
      and, in the latter model, with reduced efficiency relative to wild-type virus. 
      Rescuant viruses DoriL-I(LR)-R and DoriS-I-R behaved like wild-type virus in all 
      tests. These findings demonstrate that functional differences exist between oriL 
      and oriS and reveal a prominent role for oriL in HSV-1 pathogenesis.
FAU - Balliet, John W
AU  - Balliet JW
AD  - Department of Medicine, Harvard Medical School at the Beth Israel Deaconess 
      Medical Center, 330 Brookline Avenue, RN 123, Boston, MA 02215, USA.
FAU - Schaffer, Priscilla A
AU  - Schaffer PA
LA  - eng
GR  - R01 AI28537/AI/NIAID NIH HHS/United States
GR  - R01 AI028537/AI/NIAID NIH HHS/United States
GR  - F32 AI010557/AI/NIAID NIH HHS/United States
GR  - P01 NS35138/NS/NINDS NIH HHS/United States
GR  - P01 NS035138/NS/NINDS NIH HHS/United States
GR  - F32 AI10557/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (DNA, Viral)
SB  - IM
MH  - Animals
MH  - Chlorocebus aethiops
MH  - DNA Replication/physiology
MH  - DNA, Viral/biosynthesis/genetics
MH  - Herpes Simplex/virology
MH  - Herpesvirus 1, Human/genetics/metabolism/*pathogenicity/physiology
MH  - Humans
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Point Mutation
MH  - Replication Origin/*genetics/physiology
MH  - Vero Cells
MH  - Virus Activation
MH  - Virus Latency/*genetics/physiology
PMC - PMC1317542
EDAT- 2005/12/15 09:00
MHDA- 2007/01/27 09:00
PMCR- 2006/05/01
CRDT- 2005/12/15 09:00
PHST- 2005/12/15 09:00 [pubmed]
PHST- 2007/01/27 09:00 [medline]
PHST- 2005/12/15 09:00 [entrez]
PHST- 2006/05/01 00:00 [pmc-release]
AID - 80/1/440 [pii]
AID - 1523-05 [pii]
AID - 10.1128/JVI.80.1.440-450.2006 [doi]
PST - ppublish
SO  - J Virol. 2006 Jan;80(1):440-50. doi: 10.1128/JVI.80.1.440-450.2006.