Intracellular processing of human herpesvirus 6 glycoproteins Q1 and Q2 into tetrameric complexes expressed on the viral envelope
Intracellular processing of human herpesvirus 6 glycoproteins Q1 and Q2 into tetrameric complexes expressed on the viral envelope
复制标题
DOI：
10.1128/jvi.78.15.7969-7983.2004
复制
发表时间：
2004-08-01
影响因子：
5.4
通讯作者：
Yamanishi, K
中科院分区：
文献类型：
--
作者：
Akkapaiboon, P;Mori, Y;Yamanishi, K
人疱疹病毒6型（HHV-6）糖蛋白H和L（分别为gH和gL）与80-kDa形式的糖蛋白Q（gQ-80 K）形成异源三聚体复合物，该复合物存在于病毒包膜上，是人CD 46的病毒配体。除了gQ-80 K之外，gQ基因还编码成熟分子量为37 kDa的另外的产物（gQ-37 K），并且其源自不同的转录物。因此，我们将gQ-80 K命名为gQ 1，将gQ-37 K命名为gQ 2。我们在此表明，gQ 2也与HHV-6感染的细胞和病毒体中的gH-gL-gQl复合物相互作用。为了研究这些成分如何在HHV-6感染的细胞中相互作用，我们进行了脉冲追踪研究。结果表明，在脉冲周期的30分钟内，对内切-β-N-乙酰氨基葡糖苷酶H敏感且为gQ 2 - 37 K的前体形式的gQ 2 - 34 K与为gQ 1 - 80 K的前体形式的gQ 1 - 74 K缔合。在1小时追踪后，这些前体形式与gH-gL二聚体结合。有趣的是，抗gH单克隆抗体主要与gQ 1 - 80 K和gQ 2 - 37 K共免疫沉淀，而与gQ 1 - 74 K或gQ 2 - 34 K共免疫沉淀很少。这些结果表明，虽然gQ 2 - 34 K和gQ 1 - 74 K在内质网中相互作用，但gH-gL-gQ 1 - 80 K-gQ 2 - 37 K异源四聚体复合物在内质网后区室中产生。成熟的复合物随后被掺入病毒颗粒中。
Human herpesvirus 6 (HHV-6) glycoproteins H and L (gH and gL, respectively) and the 80-kDa form of glycoprotein Q (gQ-80K) form a heterotrimeric complex that is found on the viral envelope and that is a viral ligand for human CD46. Besides gQ-80K, the gQ gene encodes an additional product whose mature molecular mass is 37 kDa (gQ-37K) and which is derived from a different transcript. Therefore, we designated gQ-80K as gQ1 and gQ-37K as gQ2. We show here that gQ2 also interacts with the gH-gL-gQl complex in HHV-6-infected cells and in virions. To examine how these components interact in HHV-6-infected cells, we performed pulse-chase studies. The results demonstrated that gQ2-34K, which is endo-beta-N-acetylglucosaminidase H sensitive and which is the precursor form of gQ2-37K, associates with gQ1-74K, which is the precursor form of gQ1-80K, within 30 min of the pulse period. After a 1-h chase, these precursor forms had associated with the gH-gL dimer. Interestingly, an anti-gH monoclonal antibody coimmunoprecipitated mainly gQ1-80K and gQ2-37K, with little gQ1-74K or gQ2-34K. These results indicate that although gQ2-34K and gQ1-74K interact in the endoplasmic reticulum, the gH-gL-gQ1-80K-gQ2-37K heterotetrameric complex arises in the post-endoplasmic reticulum compartment. The mature complex is subsequently incorporated into viral particles.