Murine gammaherpesvirus-68 ORF38 encodes a tegument protein and is packaged into virions during secondary envelopment.
Murine gammaherpesvirus-68 ORF38 encodes a tegument protein and is packaged into virions during secondary envelopment.
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鼠伽马疱疹病毒 68 ORF38 编码一种外皮蛋白，并在二次包膜过程中被包装成病毒体
DOI：
10.1007/s13238-013-0005-0
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发表时间：
2014-02
期刊：
影响因子：
21.1
通讯作者：
Deng, Hongyu
中科院分区：
文献类型：
--
作者：
Shen, Sheng;Guo, Haitao;Deng, Hongyu
外皮是疱疹病毒体的独特结构，占据核衣壳和包膜之间的空间。越来越多的数据表明，外皮蛋白之间的相互作用在病毒颗粒形态发生中发挥着关键作用。由于细胞培养中缺乏有效的从头裂解复制，人们对包括卡波西肉瘤相关疱疹病毒 (KSHV) 和 Epstein-Barr 病毒 (EBV) 在内的伽玛疱疹病毒的形态发生知之甚少。鼠伽马疱疹病毒 68 (MHV-68) 与这两种人类疱疹病毒在遗传上相关，可作为研究伽马疱疹病毒裂解复制的有效模型。我们之前表明，MHV-68 的 ORF33 编码一种外皮蛋白，并在细胞质中病毒颗粒的成熟中发挥重要作用。然而，ORF33如何参与病毒颗粒形态发生的分子机制尚未阐明。在这项研究中，我们证明 MHV-68 的 ORF38 也是一种被膜蛋白，并且在瞬时转染和病毒感染期间定位于细胞质区室。免疫金标记分析显示ORF38仅存在于已进入细胞质囊泡的病毒体上，表明ORF38在二次包膜过程中被包装到病毒体中。我们进一步表明，在病毒感染过程中，ORF38 与 ORF33 共定位；因此，ORF38 和 ORF33 之间的相互作用在疱疹病毒中是保守的。值得注意的是，我们发现虽然 ORF33 本身分布在细胞核和细胞质中，但在 ORF38 存在的情况下，ORF33 共定位于跨高尔基体网络 (TGN)，这是发生二次包膜的位点。
Tegument is the unique structure of a herpesvirion which occupies the space between nucleocapsid and envelope. Accumulating data have indicated that interactions among tegument proteins play a key role in virion morphogenesis. Morphogenesis of gammaherpesviruses including Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) is poorly understood due to the lack of efficient de novo lytic replication in cell culture. Murine gammaherpesvirus-68 (MHV-68) is genetically related to these two human herpesviruses and serves as an effective model to study the lytic replication of gammaherpesviruses. We previously showed that ORF33 of MHV-68 encodes a tegument protein and plays an essential role in virion maturation in the cytoplasm. However, the molecular mechanism of how ORF33 participates in virion morphogenesis has not been elucidated. In this study we demonstrated that ORF38 of MHV-68 is also a tegument protein and is localized to cytoplasmic compartments during both transient transfection and viral infection. Immuno-gold labeling assay showed that ORF38 is only present on virions that have entered the cytoplasmic vesicles, indicating that ORF38 is packaged into virions during secondary envelopment. We further showed that ORF38 co-localizes with ORF33 during viral infection; therefore, the interaction between ORF38 and ORF33 is conserved among herpesviruses. Notably, we found that although ORF33 by itself is distributed in both the nucleus and the cytoplasm, in the presence of ORF38, ORF33 is co-localized to trans-Golgi network (TGN), a site where secondary envelopment takes place.
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