Role of the protein kinase PKR in the inhibition of varicella-zoster virus replication by beta interferon and gamma interferon.
Varicella-zoster virus (VZV) is sensitive to type I and type II interferons (IFNs), which mediate antiviral effects. In this study, it was demonstrated that IFN-beta and IFN-gamma inhibited the replication of VZV in vitro. Although IFN-beta was more effective than IFN-gamma, the level of inhibition of VZV replication achieved by the combination of both IFNs was more than additive and it was concluded that these two cytokines acted synergistically. Expression of the IFN-induced, double-stranded RNA-activated protein kinase PKR and its phosphorylation level were not modulated strongly during ongoing replication of VZV. However, in the presence of IFN-beta, but not IFN-gamma, PKR expression and its phosphorylation were increased, explaining in part the inhibition of virus replication by IFNs. The expression of herpes simplex virus Us11, a viral protein with several functions, including prevention of PKR activation, strongly increased the level of VZV replication.
Desloges
Nathalie
N
University of Witten/Herdecke, Institute of Microbiology and Virology, Stockumer Str. 10, D-58448 Witten, Germany.
Rahaus
Markus
M
University of Witten/Herdecke, Institute of Microbiology and Virology, Stockumer Str. 10, D-58448 Witten, Germany.
Wolff
Manfred H
MH
University of Witten/Herdecke, Institute of Microbiology and Virology, Stockumer Str. 10, D-58448 Witten, Germany.
D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D014645:Herpesvirus 3, Human / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D010766:Phosphorylation; D016601:RNA-Binding Proteins / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects*; D019892:eIF-2 Kinase / Q000378:metabolism / Q000502:physiology*
D000998:Antiviral Agents; D016601:RNA-Binding Proteins; C074546:US11 protein, herpesvirus; D014764:Viral Proteins; D016899:Interferon-beta; D007371:Interferon-gamma; D019892:eIF-2 Kinase