PMID- 10623759
OWN - NLM
STAT- MEDLINE
DCOM- 20000208
LR  - 20190508
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 74
IP  - 2
DP  - 2000 Jan
TI  - Replication of herpes simplex virus type 1 within trigeminal ganglia is required 
      for high frequency but not high viral genome copy number latency.
PG  - 965-74
AB  - The replication properties of a thymidine kinase-negative (TK(-)) mutant of 
      herpes simplex virus type 1 (HSV-1) were exploited to examine the relative 
      contributions of replication at the body surface and within trigeminal ganglia 
      (TG) on the establishment of latent infections. The replication of a TK(-) 
      mutant, 17/tBTK(-), was reduced by approximately 12-fold on the mouse cornea 
      compared to the rescued isolate 17/tBRTK(+), and no replication of 17/tBTK(-) in 
      the TG of these mice was detected. About 1.8% of the TG neurons of mice infected 
      with 17/tBTK(-) harbored the latent viral genome compared to 23% of those 
      infected with 17/tBRTK(+). In addition, the latent sites established by the TK(-) 
      mutant contained fewer copies of the HSV-1 genome (average, 2.3/neuron versus 
      28/neuron). On the snout, sustained robust replication of 17tBTK(-) in the 
      absence of significant replication within the TG resulted in a modest increase in 
      the number of latent sites. Importantly, these latently infected neurons 
      displayed a wild-type latent-genome copy number profile, with some neurons 
      containing hundreds of copies of the TK(-) mutant genome. As expected, the 
      replication of the TK(-) mutant appeared to be blocked prior to DNA replication 
      in most ganglionic neurons in that (i) virus replication was severely restricted 
      in ganglia, (ii) the number of neurons expressing HSV proteins was reduced 
      30-fold compared to the rescued isolate, (iii) cell-to-cell spread of virus was 
      not detected within ganglia, and (iv) the proportion of infected neurons 
      expressing late proteins was reduced by 89% compared to the rescued strain. These 
      results demonstrate that the viral TK gene is required for the efficient 
      establishment of latency. This requirement appears to be primarily for efficient 
      replication within the ganglion, which leads to a sixfold increase in the number 
      of latent sites established. Further, latent sites with high genome copy number 
      can be established in the absence of significant virus genome replication in 
      neurons. This suggests that neurons can be infected by many HSV virions and still 
      enter the latent state.
FAU - Thompson, R L
AU  - Thompson RL
AD  - Department of Molecular Genetics, Microbiology, and Biochemistry, University of 
      Cincinnati Medical Center, Cincinnati, Ohio 45267-0524, USA.
FAU - Sawtell, N M
AU  - Sawtell NM
LA  - eng
GR  - R01 AI032121/AI/NIAID NIH HHS/United States
GR  - AI32121/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 (Capsid Proteins)
RN  - 0 (DNA, Viral)
RN  - 0 (Herpes Simplex Virus Protein Vmw65)
RN  - 0 (ICP5 capsid protein, herpes simplex virus type 1)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (UL24 protein, Human herpesvirus 1)
RN  - 0 (Viral Proteins)
RN  - 0 (herpes simplex virus, type 1 protein ICP4)
RN  - EC 2.7.1.21 (Thymidine Kinase)
SB  - IM
EIN - J Virol. 2000 Dec;74(24):12003
MH  - Animals
MH  - Capsid/biosynthesis
MH  - *Capsid Proteins
MH  - DNA Replication
MH  - DNA, Viral/biosynthesis
MH  - Gene Deletion
MH  - Gene Dosage
MH  - Genome, Viral
MH  - Herpes Simplex Virus Protein Vmw65/biosynthesis
MH  - Herpesvirus 1, Human/genetics/*physiology
MH  - Humans
MH  - Immediate-Early Proteins/biosynthesis
MH  - Male
MH  - Mice
MH  - Neurons/virology
MH  - Rabbits
MH  - Thymidine Kinase/genetics
MH  - Trigeminal Ganglion/*virology
MH  - Viral Proteins/genetics
MH  - *Virus Latency
MH  - *Virus Replication
PMC - PMC111617
EDAT- 2000/01/07 00:00
MHDA- 2000/01/07 00:01
PMCR- 2000/01/01
CRDT- 2000/01/07 00:00
PHST- 2000/01/07 00:00 [pubmed]
PHST- 2000/01/07 00:01 [medline]
PHST- 2000/01/07 00:00 [entrez]
PHST- 2000/01/01 00:00 [pmc-release]
AID - 0790 [pii]
AID - 10.1128/jvi.74.2.965-974.2000 [doi]
PST - ppublish
SO  - J Virol. 2000 Jan;74(2):965-74. doi: 10.1128/jvi.74.2.965-974.2000.