PMID- 20071482
OWN - NLM
STAT- MEDLINE
DCOM- 20100430
LR  - 20191210
IS  - 1465-2099 (Electronic)
IS  - 0022-1317 (Linking)
VI  - 91
IP  - Pt 5
DP  - 2010 May
TI  - Differential importance of highly conserved residues in UL24 for herpes simplex 
      virus 1 replication in vivo and reactivation.
PG  - 1109-16
LID - 10.1099/vir.0.017921-0 [doi]
AB  - The UL24 gene of herpes simplex virus 1 (HSV-1) is widely conserved among all 
      subfamilies of the Herpesviridae. It is one of only four HSV-1 genes for which 
      mutations have been mapped that confer a syncytial plaque phenotype. In a mouse 
      model of infection, UL24-deficient viruses exhibit reduced titres, particularly 
      in neurons, and an apparent defect in reactivation from latency. There are 
      several highly conserved residues in UL24; however, their importance in the role 
      of UL24 in vivo is unknown. In this study, we compared virus strains with 
      substitution mutations corresponding to the PD-(D/E)XK endonuclease motif of UL24 
      (vUL24-E99A/K101A) or a substitution of another highly conserved residue 
      (vUL24-G121A). Both mutant viruses cause the formation of syncytial plaques at 39 
      degrees C; however, we found that the viruses differed dramatically when tested 
      in a mouse model of infection. vUL24-E99A/K101A exhibited titres in the eye that 
      were 10-fold lower than those of the wild-type virus KOS, and titres in 
      trigeminal ganglia (TG) that were more than 2 log10 lower. Clinical signs were 
      barely detectable with vUL24-E99A/K101A. Furthermore, the percentage of TG from 
      which virus reactivated was also significantly lower for this mutant than for 
      KOS. In contrast, vUL24-G121A behaved similarly to the wild-type virus in mice. 
      These results are consistent with the endonuclease motif being important for the 
      role of UL24 in vivo and also imply that the UL24 temperature-dependent syncytial 
      plaque phenotype can be separated genetically from several in vivo phenotypes.
FAU - Leiva-Torres, Gabriel Andre
AU  - Leiva-Torres GA
AD  - INRS-Institut Armand-Frappier, Universite du Quebec, 531 boul. des Prairies, 
      Laval, Quebec, Canada.
FAU - Rochette, Pierre-Alexandre
AU  - Rochette PA
FAU - Pearson, Angela
AU  - Pearson A
LA  - eng
GR  - 9991/Canadian Institutes of Health Research/Canada
GR  - MOP 82924/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100113
PL  - England
TA  - J Gen Virol
JT  - The Journal of general virology
JID - 0077340
RN  - 0 (Mutant Proteins)
RN  - 0 (UL24 protein, Human herpesvirus 1)
RN  - 0 (Viral Proteins)
SB  - IM
MH  - Amino Acid Substitution/genetics
MH  - Animals
MH  - Chlorocebus aethiops
MH  - Conserved Sequence
MH  - Disease Models, Animal
MH  - Eye/virology
MH  - Herpes Simplex/pathology/virology
MH  - Herpesvirus 1, Human/genetics/pathogenicity/*physiology
MH  - Mice
MH  - Mutagenesis, Site-Directed
MH  - Mutant Proteins/genetics/physiology
MH  - Severity of Illness Index
MH  - Trigeminal Ganglion/virology
MH  - Vero Cells
MH  - Viral Load
MH  - Viral Proteins/genetics/*physiology
MH  - *Virus Activation
MH  - *Virus Replication
EDAT- 2010/01/15 06:00
MHDA- 2010/05/01 06:00
CRDT- 2010/01/15 06:00
PHST- 2010/01/15 06:00 [entrez]
PHST- 2010/01/15 06:00 [pubmed]
PHST- 2010/05/01 06:00 [medline]
AID - vir.0.017921-0 [pii]
AID - 10.1099/vir.0.017921-0 [doi]
PST - ppublish
SO  - J Gen Virol. 2010 May;91(Pt 5):1109-16. doi: 10.1099/vir.0.017921-0. Epub 2010 
      Jan 13.