Transgenic Mouse with the Herpes Simplex Virus Type 1 Latency-Associated Gene: Expression and Function of the Transgene

Nurith Mador; Efrat Braun; Hillel Haim; Ilana Ariel; Amos Panet; Israel Steiner

doi:10.1128/JVI.77.23.12421-12429.2003

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Transgenic Mouse with the Herpes Simplex Virus Type 1 Latency-Associated Gene: Expression and Function of the Transgene

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Transgenic Mouse with the Herpes Simplex Virus Type 1 Latency-Associated Gene: Expression and Function of the Transgene

Nurith Mador, Efrat Braun, Hillel Haim, Ilana Ariel, Amos Panet and Israel Steiner

Journal of virology, Vol.77(23), pp.12421-12429

12/2003

DOI: 10.1128/JVI.77.23.12421-12429.2003

PMCID: PMC262558

PMID: 14610166

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Abstract

During herpes simplex virus type 1 (HSV-1) latent infection in human peripheral sensory ganglia, the major viral gene transcribed is the latency-associated transcript (LAT) gene. In order to facilitate the study of this gene, we generated a transgenic mouse that contains the DNA fragment that transcribes the LAT RNAs (2.0 kb and its 1.5-kb spliced transcript) under control of the cytomegalovirus promoter. The tissue distribution of these transcripts and their effects upon HSV-1 replication, latency, and reactivation in the transgenic-mouse model were examined. Different steady-state amounts of both transcripts were found in various tissues. While the highest levels of the 2.0-kb RNA were detected in heart and skeletal muscle, the 1.5-kb transcript was found at elevated levels in the brain and at much higher levels in the trigeminal ganglia (TG). Replication of both the wild-type and a LAT-negative mutant virus was suppressed in primary embryonic fibroblasts obtained from LAT-expressing transgenic mice compared to that in cells obtained from normal mice. HSV-1 DNA amounts in latently infected TG of transgenic mice were similar to those in normal mice. Reactivation of latent HSV-1 LAT-negative mutants by explant cocultivation of TG from transgenic mice was more efficient than reactivation from normal-mouse TG. Considering our present and previous results, we propose that the significantly higher steady-state level of the 1.5-kb RNA in the TG may link this transcript to latency functions and that by inhibition of virus replication, the LAT gene may protect ganglion cells and thereby increase the probability of reactivation.

Virus-Cell Interactions

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Title: Subtitle: Transgenic Mouse with the Herpes Simplex Virus Type 1 Latency-Associated Gene: Expression and Function of the Transgene
Creators: Nurith Mador - Clinical Virology Unit
Efrat Braun - Clinical Virology Unit
Hillel Haim - Clinical Virology Unit
Ilana Ariel - Clinical Virology Unit
Amos Panet - Clinical Virology Unit
Israel Steiner - Clinical Virology Unit
Resource Type: Journal article
Publication Details: Journal of virology, Vol.77(23), pp.12421-12429
DOI: 10.1128/JVI.77.23.12421-12429.2003
PMID: 14610166
PMCID: PMC262558
NLM abbreviation: J Virol
ISSN: 0022-538X
eISSN: 1098-5514
Publisher: American Society for Microbiology
Language: English
Date published: 12/2003
Academic Unit: Microbiology and Immunology
Record Identifier: 9984083811302771

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