An HSV-1 chimeric containing HSV-2 latency associated transcript (LAT) sequences has significantly reduced adrenergic reactivation in the rabbit eye model.
OBJECTIVE
Both HSV-1 and HSV-2 express LAT during viral latency. Previous studies indicated that deletion of either LAT impairs viral reactivation from latency, but that the HSV-1 LAT confers the ability to reactivate efficiently from trigeminal ganglia onto HSV-2. We sought to determine whether the HSV-2 LAT could function in the context of HSV-1.


METHODS
A chimeric HSV-1 that expresses the HSV-2 LAT in place of both copies of its own LAT was constructed. A rescuant virus, in which the wild-type genotype was restored, was also constructed to demonstrate that any phenotypic differences between the mutant virus and wild-type virus were due to the introduced mutations rather than to inadvertent mutations elsewhere in the virus. All viruses were tested in vitro and in vivo (via inoculation of rabbit eyes and induction of reactivation via iontophoresis of epinephrine) to determine the ability of the HSV-2 LAT to substitute for the HSV-1 LAT during acute infection and reactivation from latency.


RESULTS
Substitution of the HSV-2 LAT for the HSV-1 LAT had no effect on acute replication or on the ability of the virus to cause disease in the rabbit ocular model. The ability of the mutant virus to reactivate from latency was substantially impaired relative to wild-type HSV-1.


CONCLUSIONS
The HSV-2 LAT cannot substitute for the HSV-1 LAT in promoting reactivation from HSV-1 latency from rabbit trigeminal ganglia. This is consistent with the LAT being the major determinant of site-specific HSV reactivation.
Hill
James
J
LSU Eye Center, New Orleans, LA, USA.
Patel
Amita
A
Bhattacharjee
Partha
P
Krause
Philip
P
D000818:Animals; D002678:Chimera; D004837:Epinephrine / Q000008:administration & dosage; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000502:physiology*; D018258:Herpesvirus 2, Human / Q000235:genetics*; D007478:Iontophoresis; D035683:MicroRNAs; D009154:Mutation; D011817:Rabbits; D012668:Trigeminal Ganglion / Q000821:virology*; D014764:Viral Proteins / Q000235:genetics*; D014775:Virus Activation / Q000187:drug effects / Q000235:genetics*; D017735:Virus Latency
C477254:LAT protein, Human herpesvirus 2; D035683:MicroRNAs; D014764:Viral Proteins; C477253:latency associated transcript, herpes simplex virus-1; D004837:Epinephrine