Effect of prostaglandin A and tunicamycin on rotavirus assembly
Effect of prostaglandin A and tunicamycin on rotavirus assembly
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前列腺素A和衣霉素对轮状病毒组装的影响
DOI：
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发表时间：
1999
影响因子：
6.4
通讯作者：
Oshitani
中科院分区：
文献类型：
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作者：
Suzuki;Oshitani
Editor-Superti等人[1]描述了前列腺素A1（PGA 1）抑制轮状病毒复制和非结构蛋白NSP 4糖基化以及降低病毒蛋白VP 4和VP 7水平。SA 11轮状病毒形态发生的超微结构分析表明，尽管出芽的颗粒进入内质网（ER），病毒成熟受损的PGA 1处理的细胞，与大多数病毒颗粒留在“包膜”颗粒。尽管衣霉素抑制VP 7和NSP 4的糖基化，但用衣霉素（N-连接糖基化抑制剂）处理的细胞显示了类似的形态学观察结果[2-5]。轮状病毒具有独特的形态发生，其中颗粒获得通过亚病毒颗粒出芽进入ER而形成的瞬时膜包膜[5]。这种短暂的膜丢失，成熟的双壳病毒颗粒在ER腔中获得两种外部衣壳蛋白（VP 4和VP 7）。作者认为，在PGA 1处理的细胞中，病毒从包膜颗粒成熟为双壳颗粒受到损害。然而，另一种解释是可能的。最近，我们提出了一种新的病毒成熟途径，通过胞吐样过程，可能是通过融合样机制，因此在双壳颗粒组装过程中，亚病毒颗粒（可能是单壳颗粒）在穿过ER膜的运输过程中获得外部衣壳蛋白[6，7]。由出芽过程形成的包膜随后膨胀并破裂，并且在细胞溶解期间稍后释放单壳颗粒。因此，萌芽过程可能只是作为将单壳颗粒从细胞质运输到ER腔的载体。基于我们的观察和衣霉素处理的细胞的发现[2-5]，可以想象NSP 4的糖基化对于双壳颗粒组装和调节单壳颗粒通过ER膜的转运是必不可少的[6，7]。因此，抑制NSP 4糖基化在PGA 1处理的细胞，在与衣霉素的情况下，可能是负责不仅增加包膜颗粒通过出芽过程，但也减少双壳颗粒通过胞吐样过程。我们同意Superti等人[1]的建议，即PGA 1抑制轮状病毒复制，并为寻找轮状病毒胃肠炎的有效治疗药物提供了新的视角。
To the Editor—Superti et al. [1] describe inhibition of both rotavirus replication and nonstructural protein NSP4 glycosylation as well as decrease in viral protein VP4 and VP7 levels due to prostaglandin A1 (PGA1). Ultrastructural analysis of SA11 rotavirus morphogenesis showed that despite budding of particles into the endoplasmic reticulum (ER), virus maturation was impaired in PGA1-treated cells, with most of the virus particles remaining in “enveloped” particles. Similar morphologic observations have been shown for cells treated with tunicamycin (N-linked glycosylation inhibitor), although tunicamycin inhibits glycosylation of both VP7 and NSP4 [2–5]. Rotaviruses have a unique morphogenesis in which particles obtain a transient membrane envelope that is formed by the budding of subvirus particles into the ER [5]. This transient membrane is lost, and the mature, double-shelled virus particles acquire the two outer capsid proteins (VP4 and VP7) in the ER lumen. The authors considered that in PGA1-treated cells, virus maturation from enveloped particles to double-shelled particles was impaired. However, another interpretation is possible. Recently, we proposed a novel pathway of virus maturation by an exocytosis-like process, probably by a fusion-like mechanism, so that during double-shelled particle assembly, subvirus particles (possibly single-shelled particles) acquire the outer capsid protein during their transport across the ER membrane [6, 7]. The envelope that is formed by the budding process subsequently swells and is ruptured, and single-shelled particles are released later during cytolysis. Thus the budding process may simply serve as a vehicle to transport single-shelled particles from the cytoplasm to the ER lumen. On the basis of our observations and the finding for tunicamycin-treated cells [2–5], it is conceivable that glycosylation of NSP4 is indispensable for double-shelled particle assembly and regulation of transport of single-shelled particles through the ER membrane [6, 7]. Therefore, inhibition of NSP4 glycosylation in PGA1-treated cells, as in the case with tunicamycin, could be responsible for not only the increase in enveloped particles through the budding process, but also the reduction in double-shelled particles through the exocytosis-like process. We agree with the proposal of Superti et al. [1] that PGA1 inhibits rotavirus replication and offers new perspectives in the search for effective therapeutic agents for rotavirus gastroenteritis.