Epstein-barr virus internalization and infectivity are blocked by selective protein kinase C inhibitors

1990 ◽  
Vol 45 (3) ◽  
pp. 490-493 ◽  
Author(s):  
Mara Cirone ◽  
Antonio Angeloni ◽  
Giuseppe Barile ◽  
Claudia Zompetta ◽  
Marco Venanzoni ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Epstein Barr Virus ◽  
Protein Kinase C Inhibitors ◽  
Barr Virus ◽  
Kinase C ◽  
Epstein Barr

TPA induction of Epstein-Barr virus early antigens in Raji cells is blocked by selective protein kinase-C inhibitors

1987 ◽  
Vol 40 (6) ◽  
pp. 846-849 ◽  
Author(s):  
Janis Lazdins ◽  
Claudia Zompetta ◽  
Settimio Grimaldi ◽  
Giuseppe Barile ◽  
Marco Venanzoni ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Epstein Barr Virus ◽  
Raji Cells ◽  
Protein Kinase C Inhibitors ◽  
Barr Virus ◽  
Kinase C ◽  
Epstein Barr

scholarly journals Microtubule depolymerization activates the Epstein–Barr virus lytic cycle through protein kinase C pathways in nasopharyngeal carcinoma cells

2013 ◽  
Vol 94 (12) ◽  
pp. 2750-2758 ◽  
Author(s):  
Yi-Ru Liu ◽  
Sheng-Yen Huang ◽  
Jen-Yang Chen ◽  
Lily Hui-Ching Wang
Keyword(s):  
Protein Kinase C ◽  
Life Cycle ◽  
Protein Kinase ◽  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Lytic Cycle ◽  
Barr Virus ◽  
Kinase C ◽  
Epstein Barr ◽  
In Cells

Elevated levels of antibodies against Epstein–Barr virus (EBV) and the presence of viral DNA in plasma are reliable biomarkers for the diagnosis of nasopharyngeal carcinoma (NPC) in high-prevalence areas, such as South-East Asia. The presence of these viral markers in the circulation suggests that a minimal level of virus reactivation may have occurred in an infected individual, although the underlying mechanism of reactivation remains to be elucidated. Here, we showed that treatment with nocodazole, which provokes the depolymerization of microtubules, induces the expression of two EBV lytic cycle proteins, Zta and EA-D, in EBV-positive NPC cells. This effect was independent of mitotic arrest, as viral reactivation was not abolished in cells synchronized at interphase. Notably, the induction of Zta by nocodazole was mediated by transcriptional upregulation via protein kinase C (PKC). Pre-treatment with inhibitors for PKC or its downstream signalling partners p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) abolished the nocodazole-mediated induction of Zta and EA-D. Interestingly, the effect of nocodazole, as well as colchicine and vinblastine, on lytic gene expression occurred only in NPC epithelial cells but not in cells derived from lymphocytes. These results establish a novel role of microtubule integrity in controlling the EBV life cycle through PKC and its downstream pathways, which represents a tissue-specific mechanism for controlling the life-cycle switch of EBV.

scholarly journals Impaired Protein Kinase C Activation/Translocation in Epstein-Barr Virus-infected Monocytes

2002 ◽  
Vol 277 (27) ◽  
pp. 24148-24154 ◽  
Author(s):  
Mélanie Tardif ◽  
Martin Savard ◽  
Louis Flamand ◽  
Jean Gosselin
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
Kinase C ◽  
Epstein Barr ◽  
Protein Kinase C Activation

scholarly journals Disruption of Epstein-Barr Virus Latency in the Absence of Phosphorylation of ZEBRA by Protein Kinase C

2002 ◽  
Vol 76 (22) ◽  
pp. 11199-11208 ◽  
Author(s):  
Ayman S. El-Guindy ◽  
Lee Heston ◽  
Yoshimi Endo ◽  
Myung-Sam Cho ◽  
George Miller
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Epstein Barr Virus ◽  
Lytic Cycle ◽  
Viral Gene ◽  
Barr Virus ◽  
Kinase C ◽  
Epstein Barr

ABSTRACT ZEBRA protein converts Epstein-Barr virus (EBV) infection from the latent to the lytic state. The ability of ZEBRA to activate this switch is strictly dependent on the presence of serine or threonine at residue 186 of the protein (A. Francis, T. Ragoczy, L. Gradoville, A. El-Guindy, and G. Miller, J. Virol. 72:4543-4551, 1999). We investigated whether phosphorylation of ZEBRA protein at this site by a serine-threonine protein kinase was required for activation of an early lytic cycle viral gene, BMRF1, as a marker of disruption of latency. Previous studies suggested that phosphorylation of ZEBRA at S186 by protein kinase C (PKC) activated the protein (M. Baumann, H. Mischak, S. Dammeier, W. Kolch, O. Gires, D. Pich, R. Zeidler, H. J. Delecluse, and W. Hammerschmidt, J. Virol 72:8105-8114, 1998). Two residues of ZEBRA, T159 and S186, which fit the consensus for phosphorylation by PKC, were phosphorylated in vitro by this enzyme. Several isoforms of PKC (α, β1, β2, γ, δ, and ε) phosphorylated ZEBRA. All isoforms that phosphorylated ZEBRA in vitro were blocked by bisindolylmaleimide I, a specific inhibitor of PKC. Studies in cell culture showed that phosphorylation of T159 was not required for disruption of latency in vivo, since the T159A mutant was fully functional. Moreover, the PKC inhibitor did not block the ability of ZEBRA expressed from a transfected plasmid to activate the BMRF1 downstream gene. Of greatest importance, in vivo labeling with [32P]orthophosphate showed that the tryptic phosphopeptide maps of wild-type ZEBRA, Z(S186A), and the double mutant Z(T159A/S186A) were identical. Although ZEBRA is a potential target for PKC, in the absence of PKC agonists, ZEBRA is not constitutively phosphorylated in vivo by PKC at T159 or S186. Phosphorylation of ZEBRA by PKC is not essential for the protein to disrupt EBV latency.

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