ICP0 antagonizes Stat 1-dependent repression of herpes simplex virus: implications for the regulation of viral latency.
Virol J
; 3: 44, 2006 Jun 09.
Article
en En
| MEDLINE
| ID: mdl-16764725
ABSTRACT
BACKGROUND:
The herpes simplex virus type 1 (HSV-1) ICP0 protein is an E3 ubiquitin ligase, which is encoded within the HSV-1 latency-associated locus. When ICP0 is not synthesized, the HSV-1 genome is acutely susceptible to cellular repression. Reciprocally, when ICP0 is synthesized, viral replication is efficiently initiated from virions or latent HSV-1 genomes. The current study was initiated to determine if ICP0's putative role as a viral interferon (IFN) antagonist may be relevant to the process by which ICP0 influences the balance between productive replication versus cellular repression of HSV-1.RESULTS:
Wild-type (ICP0+) strains of HSV-1 produced lethal infections in scid or rag2-/- mice. The replication of ICP0- null viruses was rapidly repressed by the innate host response of scid or rag2-/- mice, and the infected animals remained healthy for months. In contrast, rag2-/- mice that lacked the IFN-alpha/beta receptor (rag2-/- ifnar-/-) or Stat 1 (rag2-/- stat1-/-) failed to repress ICP0- viral replication, resulting in uncontrolled viral spread and death. Thus, the replication of ICP0- viruses is potently repressed in vivo by an innate immune response that is dependent on the IFN-alpha/beta receptor and the downstream transcription factor, Stat 1.CONCLUSION:
ICP0's function as a viral IFN antagonist is necessary in vivo to prevent an innate, Stat 1-dependent host response from rapidly repressing productive HSV-1 replication. This antagonistic relationship between ICP0 and the host IFN response may be relevant in regulating whether the HSV-1 genome is expressed, or silenced, in virus-infected cells in vivo. These results may also be clinically relevant. IFN-sensitive ICP0- viruses are avirulent, establish long-term latent infections, and induce an adaptive immune response that is highly protective against lethal challenge with HSV-1. Therefore, ICP0- viruses appear to possess the desired safety and efficacy profile of a live vaccine against herpetic disease.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Virales
/
Regulación Viral de la Expresión Génica
/
Latencia del Virus
/
Simplexvirus
/
Proteínas Inmediatas-Precoces
/
Ubiquitina-Proteína Ligasas
/
Factor de Transcripción STAT1
/
Herpes Simple
Límite:
Animals
Idioma:
En
Revista:
Virol J
Asunto de la revista:
VIROLOGIA
Año:
2006
Tipo del documento:
Article
País de afiliación:
Estados Unidos