Replication of varicella-zoster virus is influenced by the levels of JNK/SAPK and p38/MAPK activation.
Stimulation of the Jun NH(2)-terminal kinase/stress-activated protein kinase (JNK/SAPK) and the p38 mitogen-activated protein kinase (p38/MAPK) is part of the stress-related signal transduction pathways conveying signals from the cell surface into the nucleus in order to initiate programmes of gene expression. Here, it was shown that infection by varicella-zoster virus (VZV) caused a 34-fold increase in activation of JNK/SAPK in the early phase of infection and a 2-fold increase in activation of p38/MAPK in the later phase. The phosphorylation of downstream targets c-Jun and ATF-2 was also increased; subsequent cascades to induce pro-inflammatory responses were significantly activated whereas cascades to activate apoptotic events were not. In the late phase of infection, both JNK/SAPK and p38/MAPK activities were reduced to basal levels. The use of specific inhibitors demonstrated that inhibition of JNK/SAPK resulted in a 2-fold increase in VZV replication whereas a strong decrease in virus replication was observed after inhibition of p38/MAPK. In contrast, constitutive activation of JNK/SAPK resulted in a decline in VZV replication. Blocking gene expression by treating cells with actinomycin D or cycloheximide prior to infection resulted in activation of neither JNK/SAPK nor p38/MAPK. It was assumed that the presence of tegument proteins was not sufficient to activate stress pathways, but that expression of viral genes was necessary. This suggests that activation of stress pathways by VZV infection represents a finely regulated system that activates cellular transcription factors for transregulation of VZV-encoded genes, but prevents activation of cellular defence mechanisms.
Rahaus
Markus
M
University of Witten/Herdecke, Institute of Microbiology and Virology, Stockumer Str. 10, D-58448 Witten, Germany.
Desloges
Nathalie
N
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.
D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D004789:Enzyme Activation; D014645:Herpesvirus 3, Human / Q000235:genetics / Q000502:physiology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology*; D014779:Virus Replication; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*
D003513:Cycloheximide; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases