Neuronal activity regulates viral replication of herpes simplex virus type 1 in the nervous system.
J Neurovirol
; 11(3): 256-64, 2005 Jul.
Article
em En
| MEDLINE
| ID: mdl-16036805
ABSTRACT
Herpes simplex virus types 1 and 2 (HSV-1, -2) infect and also establish latency in neurons. In the present study, the authors investigated the influence of neuronal activity on the replication of HSV-1. The results showed that the sodium channel blocker tetrodotoxin (TTX) and the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) could significantly increase viral replication in primary neuronal cultures, by two- to fourfold. In contrast, KCl reduced viral production by at least 80% in the same cultures. Inhibitors of GABA(A) receptors completely abolished the effects of GABA. Intravitreously injected TTX in a mouse corneal scarification model enhanced the viral titers > 10-fold in both the trigeminal ganglia and the brain. At 2 h post infection, both TTX and GABA significantly up-regulated the levels of transcription for the viral immediate early (IE) genes ICP0, ICP4, and ICP27, as revealed by real time PCR. These results indicate that the neuronal excitation status may dictate the efficiency of HSV-1 viral replication, probably by regulating the levels of viral IE gene expression. These are the first findings connecting neuronal activity to the molecular mechanisms of HSV replication in the nervous system, which may significantly influence our view of herpesvirus infection and latency.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Herpesvirus Humano 1
/
Herpes Simples
/
Neurônios
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Neurovirol
Assunto da revista:
NEUROLOGIA
/
VIROLOGIA
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Canadá