Marek's disease virus oncoprotein Meq physically interacts with the chicken infectious anemia virus-encoded apoptotic protein apoptin.
Marek's disease virus oncoprotein Meq physically interacts with the chicken infectious anemia virus-encoded apoptotic protein apoptin.
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DOI：
10.18632/oncotarget.25628
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发表时间：
2018-06-22
期刊：
影响因子：
--
通讯作者：
Nair V
中科院分区：
文献类型：
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作者：
Brown AC;Reddy VRAP;Lee J;Nair V
马立克氏病（Marek's disease，MD）是由马立克氏病病毒（Marek's disease virus，MDV）引起的一种禽类肿瘤性疾病。Meq是MDV的主要癌蛋白，通过多种机制诱导T细胞的肿瘤转化，包括抑制细胞凋亡。相比之下，鸡贫血病毒（CAV）编码的蛋白VP 3是肿瘤细胞凋亡的强大诱导剂，这是一种用于抗癌治疗的特性。虽然选择性诱导肿瘤细胞凋亡的分子机制还不完全清楚，但其肿瘤细胞限制性核转位被认为是重要的。MDV和CAV的共感染在许多国家很常见，CAV抗原在MD淋巴瘤中很容易检测到，并且MDV转化的T-淋巴母细胞样细胞系如MSB-1广泛用于增殖CAV用于疫苗生产。由于MDV转化的细胞系表达高水平的Meq，我们在这里研究了CAV编码的抗病毒蛋白是否与这些细胞中的Meq相互作用。使用免疫荧光显微镜，我们发现，reflectin和Meq共定位于细胞核，和生化分析表明，这两种蛋白质的物理相互作用。使用Meq诱变和免疫共沉淀的组合，我们证明，reflectin与Meq之间的氨基酸130和140之间的区域内的相互作用。IncuCyte分析的结果表明，Meq抑制了抑制素诱导的细胞凋亡活性。总之，我们的研究结果表明，Meq相互作用和抑制rectin。深入了解Meq和Eschertin之间的这种新的相互作用将与两种病毒共感染的发病机制和使用MDV转化细胞系的CAV疫苗生产相关。
Marek's disease (MD) is a neoplastic disease of poultry caused by Marek's disease virus (MDV), a highly contagious alphaherpesvirus. Meq, the major MDV oncoprotein, induces neoplastic transformation of T-cells through several mechanisms, including inhibition of apoptosis. In contrast, the chicken anemia virus (CAV)-encoded protein apoptin (VP3) is a powerful inducer of apoptosis of tumor cells, a property that is exploited for anticancer therapeutics. Although the molecular mechanisms of selective induction of tumor cell apoptosis by apoptin are not fully understood, its tumor cell–restricted nuclear translocation is thought to be important. Co-infection with MDV and CAV is common in many countries, CAV antigens are readily detectable in MD lymphomas, and the MDV-transformed T-lymphoblastoid cell lines such as MSB-1 is widely used for propagating CAV for vaccine production. As MDV-transformed cell lines express high levels of Meq, we examined here whether CAV-encoded apoptin interacts with Meq in these cells. Using immunofluorescence microscopy, we found that apoptin and Meq co-localize to the nucleus, and biochemical analysis indicated that the two proteins do physically interact. Using a combination of Meq mutagenesis and co-immunoprecipitation, we demonstrate that apoptin interacts with Meq within a region between amino acids 130 and 140. Results from the IncuCyte assay suggested that Meq inhibits apoptin-induced apoptosis activity. In summary, our findings indicate that Meq interacts with and inhibits apoptin. Insights into this novel interaction between Meq and apoptin will relevance for pathogenesis of coinfections of the two viruses and in CAV vaccine production using MDV-transformed cell lines.