A cAMP response element within the latency-associated transcript promoter of HSV-1 facilitates induced ocular reactivation in a mouse hyperthermia model.
Herpes simplex virus type 1 (HSV-1) recombinant strain 17CRE contains a site-directed mutation in the 7-bp CRE consensus sequence located 38 nucleotides upstream of the transcription start site. Scarified mouse corneas received inoculations of 17syn+ (parent), 17CRE, and rescue 17CREr. Slit lamp examination of herpetic lesions and tear film swabs containing infectious virus showed that 17CRE had the same acute phenotype as 17syn+ and 17CREr. At 4 weeks, when the corneas had healed and latency was established, mice received hyperthermic shock. Eye swabs taken 24 h after hyperthermia showed that 17CRE reactivated significantly less than 17syn+ and 17CREr, while no significant differences were found in HSV-1 DNA genome copy numbers and latent virus in the trigeminal ganglia. These results are evidence that this CRE site in the LAT promoter facilitates ocular HSV-1 reactivation in mice.
Marquart
M E
ME
Department of Ophthalmology, Microbiology, Pharmacology, and Neuroscience, LSU Health Sciences Center, New Orleans, Louisiana, 70112, USA.
Zheng
X
X
Tran
R K
RK
Thompson
H W
HW
Bloom
D C
DC
Hill
J M
JM
D000818:Animals; D003315:Cornea / Q000821:virology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D004195:Disease Models, Animal; D018882:Heat Stress Disorders / Q000150:complications*; D018259:Herpesvirus 1, Human / Q000235:genetics*; D016849:Keratitis, Herpetic / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D016297:Mutagenesis, Site-Directed; D010641:Phenotype; D011401:Promoter Regions, Genetic; D011817:Rabbits; D012008:Recurrence; D012668:Trigeminal Ganglion / Q000821:virology; D017735:Virus Latency / Q000235:genetics*
D017362:Cyclic AMP Response Element-Binding Protein