PMID- 8627763
OWN - NLM
STAT- MEDLINE
DCOM- 19960621
LR  - 20200724
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 70
IP  - 5
DP  - 1996 May
TI  - High-dose ocular infection with a herpes simplex virus type 1 ICP34.5 deletion 
      mutant produces no corneal disease or neurovirulence yet results in wild-type 
      levels of spontaneous reactivation.
PG  - 2883-93
AB  - We report here that in the rabbit ocular model of herpes simplex virus type 1 
      (HSV-1) latency, spontaneous reactivation of the HSV-1 ICP34.5 deletion mutant 
      d34.5 increased significantly in response to increasing infectious doses. At the 
      highest infectious dose of d34.5, the spontaneous reactivation rate was 
      indistinguishable from that of wild-type virus (average spontaneous reactivation 
      rates for d34.5, 0.3 to 1.4% at 2 x 10(5) PFU per eye, 3.4% at 2 x 10(6) PFU per 
      eye, and 6.3 to 11.5% at 1 x 10(8) PFU per eye; average spontaneous reactivation 
      rates for marker-rescued virus, 7.7 to 19.6% at 2 x 10(5) PFU per eye). The 
      percentage of latency-associated transcript (LAT) RNA-positive neurons in 
      sections from trigeminal ganglia (TG) of rabbits latently infected with d34.5 
      demonstrated a similar dose-response effect as estimated by in situ hybridization 
      (0.05% LAT RNA-positive neurons at 2 x 10(5) PFU per eye and 0.1% LAT 
      RNA-positive neurons at 1 x 10(8) PFU per eye; P = 0.002). In contrast, even at 
      the highest infectious dose (1 x 10(8) PFU per eye), d34.5 was less virulent (23 
      of 23 survivors) than the normal infectious dose (2 x 10(5) PFU per eye) of 
      marker-rescued virus (14 of 27 survivors; P < 0.0001). In addition, at 1 x 10(8) 
      PFU per eye, d34.5 produced virtually no corneal disease, compared with the 
      production of severe corneal disease by 2 x 10(5) PFU of marker-rescued virus per 
      eye (P < 0.0001). Thus, at increasing infectious doses of d34.5, both spontaneous 
      reactivation and the percentage of neurons expressing LAT appeared to increase, 
      without a corresponding increase in virulence. These results strongly suggest 
      that (i) the phenotypes of neurovirulence and spontaneous reactivation are 
      separable, (ii) the phenotypes of corneal disease and spontaneous reactivation 
      are separable, and (iii) the decreased rate of spontaneous reactivation 
      previously reported for d34.5 (G. C. Perng, R. L. Thompson, N. M. Sawtell, W. E. 
      Taylor, S. M. Slanina, H. Ghiasi, R. Kaiwar, A. B. Nesburn, and S. L. Wechsler, 
      J. Virol. 69:3033-3041, 1995) is at least partially due to a reduced rate of 
      establishing latency.
FAU - Perng, G C
AU  - Perng GC
AD  - Ophthalmology Research Laboratories, Cedars-Sinai Medical Center, Los Angeles, 
      California, USA.
FAU - Ghiasi, H
AU  - Ghiasi H
FAU - Slanina, S M
AU  - Slanina SM
FAU - Nesburn, A B
AU  - Nesburn AB
FAU - Wechsler, S L
AU  - Wechsler SL
LA  - eng
GR  - EY07566/EY/NEI NIH HHS/United States
GR  - EY10243/EY/NEI NIH HHS/United States
PT  - Comparative Study
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 (RNA, Viral)
RN  - 0 (Viral Proteins)
RN  - 0 (gamma 34.5 protein, Human herpesvirus 1)
SB  - IM
MH  - Animals
MH  - Cornea/pathology/*virology
MH  - *Gene Deletion
MH  - In Situ Hybridization
MH  - Keratitis, Herpetic/pathology/*physiopathology
MH  - Neurons/pathology/*virology
MH  - RNA, Viral/analysis/biosynthesis
MH  - Rabbits
MH  - Simplexvirus/genetics/*pathogenicity/*physiology
MH  - Species Specificity
MH  - Transcription, Genetic
MH  - Trigeminal Ganglion/pathology/*virology
MH  - Viral Proteins/*genetics
MH  - Virulence
MH  - *Virus Activation
MH  - *Virus Replication
PMC - PMC190146
EDAT- 1996/05/01 00:00
MHDA- 1996/05/01 00:01
PMCR- 1996/05/01
CRDT- 1996/05/01 00:00
PHST- 1996/05/01 00:00 [pubmed]
PHST- 1996/05/01 00:01 [medline]
PHST- 1996/05/01 00:00 [entrez]
PHST- 1996/05/01 00:00 [pmc-release]
AID - 10.1128/JVI.70.5.2883-2893.1996 [doi]
PST - ppublish
SO  - J Virol. 1996 May;70(5):2883-93. doi: 10.1128/JVI.70.5.2883-2893.1996.