Annexin 2-mediated enhancement of cytomegalovirus infection opposes inhibition by annexin 1 or annexin 5
Annexin 2-mediated enhancement of cytomegalovirus infection opposes inhibition by annexin 1 or annexin 5
复制标题
DOI：
10.1099/vir.0.82294-0
复制
发表时间：
2007-01-01
影响因子：
3.8
通讯作者：
Pryzdial, Edward L. G.
中科院分区：
文献类型：
--
作者：
Derry, Man E. C.;Sutherland, Michael R.;Pryzdial, Edward L. G.
生化研究表明膜联蛋白 2 (A2) 可能参与巨细胞病毒 (CMV) 感染。在当前的工作中，研究了 A2 单体 (p36) 和异四聚体 (A2t; p36(2)p11(2)) 的影响。为了证明内源性 A2 的作用，随后的四个感染阶段在 37 摄氏度下均受到抗 p36 或抗 p11 的抑制。当病毒和细胞在 4 摄氏度下预孵育以协调随后在 37 摄氏度下开始的病毒进入时，免疫抑制被减弱，从而调和了文献中的争议。作为解释，4 摄氏度处理阻止了 CMV 诱导的 p36 磷酸化。纯化的 A2t 或 p11 增加了 CMV 感染后代的产生和 CMV 基因表达，支持了这些免疫抑制数据。纯化的 p36 没有作用表明 A2t 具有特定作用。与其他步骤不同，纯化的 A2t 或 p11 并未增强初级噬菌斑形成，可能是因为无法检测到磷酸化。由于膜联蛋白 1 (A1) 和 5 (A5) 与 A2 相互作用，因此还测试了它们对 CMV 的影响。两种纯化的蛋白质均抑制 CMV 感染。在每个实验中，半最大抑制所需的All浓度比A5低5至10倍。 A2的添加对抗A1或A5介导的CMV抑制，某些A2特异性抗体在不添加A1或A5的情况下没有效果也是如此。 p36 缺陷细胞系 HepG2 的转染增加了 CMV 感染，并且是其他膜联蛋白抑制所必需的。这些数据表明CMV在生理温度下利用A2t来对抗All或A5赋予细胞的保护。
Biochemical studies have suggested that annexin 2 (A2) may participate in cytomegalovirus (CMV) infection. In the current work, effects of A2 monomer (p36) and heterotetramer (A2t; p36(2)p11(2)) were investigated. Demonstrating a role for endogenous A2, the four stages of infection that were followed were each inhibited by anti-p36 or anti-p11 at 37 degrees C. Immuno-inhibition was attenuated when the virus and cells were pre-incubated at 4 degrees C to coordinate virus entry initiated afterwards at 37 degrees C, reconciling controversy in the literature. As an explanation, CMV-induced phosphorylation of p36 was prevented by the 4 degrees C treatment. Supporting these immuno-inhibition data, purified A2t or p11 increased CMV infectious-progeny generation and CMV gene expression. A specific role for A2t was indicated by purified p36 having no effect. Unlike other steps, primary plaque formation was not enhanced by purified A2t or p11, possibly because of undetectable phosphorylation. As annexins 1 (A1) and 5 (A5) interact with A2, their effect on CMV was also tested. Both purified proteins inhibited CMV infection. In each experiment, the concentration of All required for half-maximal inhibition was five- to 10-fold lower than that of A5. Addition of A2 opposed A1- or A5-mediated inhibition of CMV, as did certain A2-specific antibodies that had no effect in the absence of added All or A5. Transfection of the p36-deficient cell line HepG2 increased CMV infection and was required for inhibition by the other annexins. These data suggest that CMV exploits A2t at physiological temperature to oppose the protection of cells conferred by All or A5.