Impaired protein kinase C activation/translocation in Epstein-Barr virus-infected monocytes.
Infection of human monocytes by Epstein-Barr virus (EBV) has been linked to a decrease in the production of proinflammatory mediators as well as an impairment of phagocytosis. Considering the key role of protein kinases C (PKCs) in many biological functions of monocytes, including phagocytosis, we investigated the effects of EBV on the PKC activity in infected monocytes. Our results indicate that infection of monocytes by EBV impairs both phorbol 12-myristate 13-acetate (PMA)-induced translocation of PKC isozymes alpha and beta from cytosol to membrane as well as the PKC enzymatic activity. Similarly, the subcellular distribution of the receptor for activated C kinase (RACK), an anchoring protein essential to PKC translocation, was also found to be reduced in EBV-infected monocytes. Transfection of 293T cells with an expression vector coding for the immediate-early protein ZEBRA of EBV resulted in impaired PMA-induced translocation and activity of PKC. Using co-immunoprecipitation assays, the ZEBRA protein was found to physically interact with the RACK1 protein. Thus interaction of ZEBRA with RACK likely results in the inhibition of PKC activity, which in turn affects functions of monocytes, such as phagocytosis.
Tardif
Melanie
M
Laboratory of Viral Immunology, Laboratory of Virology, Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du Centre Hospitalier de l'Université Laval, and Université Laval, Québec G1V 4G2, Canada.
Savard
Martin
M
Flamand
Louis
L
Gosselin
Jean
J
D002462:Cell Membrane / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D004268:DNA-Binding Proteins / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D009000:Monocytes / Q000502:physiology* / Q000821:virology; D009281:Naphthalenes / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000097:blood*; D021381:Protein Transport; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D015534:Trans-Activators / Q000097:blood; D014764:Viral Proteins
C063676:BZLF1 protein, Herpesvirus 4, Human; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D007211:Indoles; D009281:Naphthalenes; D015534:Trans-Activators; D014764:Viral Proteins; D011493:Protein Kinase C; C058819:calphostin C; D013755:Tetradecanoylphorbol Acetate; C064758:Ro 31-8220