title: The latency-associated transcript gene enhances establishment of herpes simplex virus type 1 latency in rabbits.
abstract: The latency-associated transcript (LAT) gene the only herpes simplex virus type 1 (HSV-1) gene abundantly transcribed during neuronal latency, is essential for efficient in vivo reactivation. Whether LAT increases reactivation by a direct effect on the reactivation process or whether it does so by increasing the establishment of latency, thereby making more latently infected neurons available for reactivation, is unclear. In mice, LAT-negative mutants appear to establish latency in fewer neurons than does wild-type HSV-1. However, this has not been confirmed in the rabbit, and the role of LAT in the establishment of latency remains controversial. To pursue this question, we inserted the gene for the enhanced green fluorescent protein (EGFP) under control of the LAT promoter in a LAT-negative virus (DeltaLAT-EGFP) and in a LAT-positive virus (LAT-EGFP). Sixty days after ocular infection, trigeminal ganglia (TG) were removed from the latently infected rabbits, sectioned, and examined by fluorescence microscopy. EGFP was detected in significantly more LAT-EGFP-infected neurons than DeltaLAT-EGFP-infected neurons (4.9% versus 2%, P < 0.0001). The percentages of EGFP-positive neurons per TG ranged from 0 to 4.6 for DeltaLAT-EGFP and from 2.5 to 11.1 for LAT-EGFP (P = 0.003). Thus, LAT appeared to increase neuronal latency in rabbit TG by an average of two- to threefold. These results suggest that LAT enhances the establishment of latency in rabbits and that this may be one of the mechanisms by which LAT enhances spontaneous reactivation. These results do not rule out additional LAT functions that may be involved in maintenance of latency and/or reactivation from latency.
authors.affiliation: Ophthalmology Research Laboratories, Cedars-Sinai Medical Center Burns & Allen Research Institute, Los Angeles, California 90048, USA.
authors.forename: G C
authors.initials: GC
authors.lastname: Perng
authors.forename: S M
authors.initials: SM
authors.lastname: Slanina
authors.forename: A
authors.initials: A
authors.lastname: Yukht
authors.forename: H
authors.initials: H
authors.lastname: Ghiasi
authors.forename: A B
authors.initials: AB
authors.lastname: Nesburn
authors.forename: S L
authors.initials: SL
authors.lastname: Wechsler
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D005814:Genes, Viral; D049452:Green Fluorescent Proteins; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics; D009474:Neurons / Q000821:virology; D011401:Promoter Regions, Genetic; D011817:Rabbits; D012668:Trigeminal Ganglion / Q000821:virology; D017735:Virus Latency; D014779:Virus Replication
chemical_list: D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins