Herpes simplex virus latent phase transcription facilitates in vivo reactivation.
The biological role of latent phase transcripts was studied in a rabbit model of herpes simplex virus type I (HSV-I) ocular reactivation. Virus X10-13, a variant of HSV which does not express latency associated transcripts (LAT), has been previously shown to establish latent infection in mouse sensory nerve ganglia, and LAT(-) virus can be recovered upon explantation and cocultivation of ganglia. In the rabbit, we show here that this virus replicates normally on the cornea and conjunctiva and establishes latent infections in corresponding trigeminal ganglionic neurons. However, X10-13 is not efficiently reactivated after iontophoresis of 0.01% epinephrine into the cornea. In contrast, XC-20, a LAT(+) derivative of X10-13 in which LAT expression had been restored by marker rescue of X10-13 with a cloned HSV-I EcoRI J + K fragment, reactivated at a significantly higher rate. Control experiments indicated that XC-20 and X10-13 established latent infections in an equivalent number of neurons. We conclude that latent phase transcription of HSV facilitates ganglionic reactivation and subsequent ocular shedding of the reactivated virus.
Hill
J M
JM
Lions Eye Research Laboratories, Louisiana State University Medical Center, New Orleans 70112.
Sedarati
F
F
Javier
R T
RT
Wagner
E K
EK
Stevens
J G
JG
D000208:Acute Disease; D000818:Animals; D015152:Blotting, Northern; D003228:Conjunctiva / Q000382:microbiology; D003315:Cornea / Q000382:microbiology; D015342:DNA Probes; D007635:Keratitis, Dendritic / Q000382:microbiology*; D009474:Neurons / Q000382:microbiology; D009693:Nucleic Acid Hybridization; D011817:Rabbits; D012008:Recurrence; D018139:Simplexvirus / Q000235:genetics* / Q000502:physiology; D014158:Transcription, Genetic; D012668:Trigeminal Ganglion / Q000382:microbiology; D014779:Virus Replication
D015342:DNA Probes