Interaction of JC virus Agno protein with T antigen modulates transcription and replication of the viral genome in glial cells
Interaction of JC virus Agno protein with T antigen modulates transcription and replication of the viral genome in glial cells
复制标题
DOI：
10.1128/jvi.75.3.1476-1486.2001
复制
发表时间：
2001-02-01
影响因子：
5.4
通讯作者：
Khalili, K
中科院分区：
文献类型：
--
作者：
Safak, M;Barrucco, R;Khalili, K
除了编码结构蛋白和调节蛋白外，许多病毒还编码辅助蛋白，其中一些已被证明在病毒的裂解和潜伏状态中起重要作用。人类嗜神经JC病毒（JCV）基因组编码一种称为阿尼奥的辅助蛋白，其功能尚不清楚。在这里，我们研究了JCV阿尼奥蛋白在神经胶质细胞中对病毒基因组转录和复制的功能作用。转染人神经胶质细胞的结果表明，阿尼奥蛋白抑制T抗原介导的病毒晚期基因启动子的转录和T抗原诱导的病毒DNA复制。亲和层析和免疫共沉淀试验表明，阿尼奥蛋白和T抗原的物理相互作用。通过使用一系列的缺失突变体，我们证明了T抗原相互作用区域的阿尼奥蛋白定位于其氨基末端的一半和Agno相互作用域的T抗原映射到其中央部分。此外，在功能研究中利用各种阿尼奥缺失突变体，我们证实了Agno-T抗原相互作用在观察到的阿尼奥蛋白下调病毒基因转录和DNA复制后的T抗原功能中的重要性。总之，这些数据表明，JCV的阿尼奥蛋白，其在裂解周期的晚期产生，可以与病毒早期蛋白，T抗原，物理和功能相互作用，并下调病毒基因表达和DNA复制。这些意见在溶解周期的JCV的重要性进行了讨论。
In addition to encoding the structural and regulatory proteins, many viruses encode auxiliary proteins, some of which have been shown to pig important roles in lytic and latent states of the viruses. The human neurotropic JC virus (JCV) genome encodes an auxiliary protein called Agno whose function remains unknown. Here, we investigated the functional role of JCV Agno protein on transcription and replication of the viral genome in glial cells. Results from transfection of human glial cells shelved that Agno protein suppresses both T-antigen-mediated transcription of the viral late gene promoter and T-antigen-induced replication of viral DNA. Affinity chromatography and coimmunoprecipitation assays demonstrated that the Agno protein and T antigen physically interact with each other. Through the use of a series of deletion mutants, we demonstrated that the T-antigen-interacting region of Agno protein is localized to its amino-terminal half and the Agno-interacting domain of T antigen maps to its central portion. Furthermore, utilizing various Agno deletion mutants in functional studies, we confirmed the importance of the Agno-T antigen interaction in the abserved down-modulation of T antigen function upon viral gene transcription and DNA replication by Agno protein. Taken together these data suggest that the Agno protein of JCV, which is produced late during the late phase of the lytic cycle, can physically and functionally interact with the viral early protein, T antigen, and downregulate viral gene expression and DNA replication. The importance of these observations in the lytic cycle of JCV is discussed.