Tardif Melanie, Savard Martin, Flamand Louis, Gosselin Jean
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.
J Biol Chem. 2002 Jul 5;277(27):24148-54. doi: 10.1074/jbc.M109036200. Epub 2002 Apr 23.
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.
爱泼斯坦-巴尔病毒（EBV）感染人类单核细胞与促炎介质产生减少以及吞噬作用受损有关。鉴于蛋白激酶C（PKC）在单核细胞的许多生物学功能（包括吞噬作用）中起关键作用，我们研究了EBV对受感染单核细胞中PKC活性的影响。我们的结果表明，EBV感染单核细胞会损害佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）诱导的PKC同工酶α和β从细胞质向细胞膜的转位以及PKC酶活性。同样，在EBV感染的单核细胞中，活化C激酶受体（RACK）（PKC转位所必需的锚定蛋白）的亚细胞分布也被发现减少。用编码EBV即刻早期蛋白ZEBRA的表达载体转染293T细胞，导致PMA诱导的PKC转位和活性受损。通过免疫共沉淀试验，发现ZEBRA蛋白与RACK1蛋白发生物理相互作用。因此，ZEBRA与RACK的相互作用可能导致PKC活性受到抑制，进而影响单核细胞的功能，如吞噬作用。
