Differential utilisation of ceramide during replication of the flaviviruses West Nile and dengue virus
Differential utilisation of ceramide during replication of the flaviviruses West Nile and dengue virus
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DOI：
10.1016/j.virol.2015.06.015
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发表时间：
2015-10-01
期刊：
影响因子：
3.7
通讯作者：
Mackenzie, Jason M.
中科院分区：
文献类型：
--
作者：
Aktepe, Turgut E.;Pham, Helen;Mackenzie, Jason M.
已经证实，+ssRNA病毒操纵细胞内脂平衡和分布，以促进有效的复制。在这里，我们发现细胞脂质神经酰胺被重新分布到西尼罗河病毒昆津病毒株(WNVKUN)复制复合体(RC)，而不是登革2型病毒新几内亚C株(DENVNGC)RC。我们发现，用麦角菌素长期化学抑制丝氨酸棕榈酰转移酶对WNVKUN复制有显著的有害影响，但促进了DENVNGC复制。此外，用伏马菌素B-1抑制神经酰胺合成酶对WNVKUN的复制和感染性病毒颗粒的释放有不利影响，但对DENVNGC的复制和病毒生产有促进作用。这些观察表明，通过新星和挽救途径产生神经酰胺是WNVKUN复制所必需的，但对DENVNGC复制是抑制的。因此，尽管这两种病毒来自同一属，但它们的复制需要不同的神经酰胺。(C)2015 Elsevier Inc.保留所有权利。
It is well established that + ssRNA viruses manipulate cellular lipid homoeostasis and distribution to facilitate efficient replication. Here, we show that the cellular lipid ceramide is redistributed to the West Nile virus strain Kunjin virus (WNVKUN) replication complex (RC) but not to the dengue virus serotype 2 strain New Guinea C (DENVNGC) RC. We show that prolonged chemical inhibition of serine palmitoyltransferase with myriocin had a significant deleterious effect on WNVKUN replication but enhanced DENVNGC replication. Additionally, inhibition of ceramide synthase with Fumonisin B-1 had a detrimental effect on WNVKUN replication and release of infectious virus particles but contrastingly an enhancing effect on DENVNGC replication and virus production. These observations suggest that ceramide production via the de nova and salvage pathway is a requirement for WNVKUN replication but inhibitory for DENVNGC replication. Thus, although these two viruses are from the same genus, they have a differential ceramide requirement for replication. (C) 2015 Elsevier Inc. All rights reserved.