Lipidomic Analysis Reveals Serum Alteration of Plasmalogens in Patients Infected With ZIKA Virus

Lipidomic Analysis Reveals Serum Alteration of Plasmalogens in Patients Infected With ZIKA Virus
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DOI:
10.3389/fmicb.2019.00753
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发表时间:
2019-04-12
影响因子:
5.2
通讯作者:
Alcantara, Luiz Carlos Junior
Alcantara, Luiz Carlos Junior
中科院分区:
生物学2区
文献类型:
--
作者:
Queiroz, Adriano;Dantas Pinto, Isabella Fernanda;Alcantara, Luiz Carlos Junior

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寨卡病毒(Zika Virus,ZIKV)是黄病毒科黄病毒属节肢动物传播病毒(虫媒病毒)。自2013-2014年法属波利尼西亚和2015年巴西爆发大规模疫情以来,ZIKV一直被视为新的公共卫生威胁。与其他相关的黄病毒相似,ZIKV与轻微的自限性症状有关,如皮疹、瘙痒、虚弱、头痛、关节痛、肌肉痛、结膜炎、下腰痛,如果出现,还会出现短期低烧。此外,ZIKV还与神经系统并发症有关,如新生儿小头畸形和成人格林-巴利综合征。在这里,血清脂组学分析被用来确定ZIKV感染引发的脂代谢的可能变化。以发热、关节痛、头痛、红肿、肌痛、瘙痒等病毒样症状患者为对照组。我们的研究揭示了ZIKV患者血清中几种磷脂酰乙醇胺(PE)脂类物种的水平升高,其中大多数是与多不饱和脂肪酸相关的质膜-磷脂酰乙醇胺(PPE)(或血浆原)。与多不饱和脂肪酸相关的血浆原占人类总磷脂的20%,在大脑的神经膜中尤其丰富。血浆原的生物合成需要功能性的过氧化物体,这是包括ZIKV在内的病毒复制的重要部位。因此,ZIKV感染者血清中血浆原水平的升高表明ZIKV的生命周期与过氧化物体之间存在联系。我们的数据为可能与ZIKV复制相关的特定宿主细胞脂质提供了重要的见解,并可能作为抗ZIKV策略的平台。
Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) in the Flavivirus genus of the Flaviviridae family. Since the large outbreaks in French Polynesia in 2013-2014 and in Brazil in 2015, ZIKV has been considered a new public health threat. Similar to other related flavivirus, ZIKV is associated with mild and self-limiting symptoms such as rash, pruritus, prostration, headache, arthralgia, myalgia, conjunctivitis, lower back pain and, when present, a short-term low grade fever. In addition, ZIKV has been implicated in neurological complications such as neonatal microcephaly and Guillain-Barre syndrome in adults. Herein, serum lipidomic analysis was used to identify possible alterations in lipid metabolism triggered by ZIKV infection. Patients who presented virus-like symptoms such as fever, arthralgia, headache, exanthema, myalgia and pruritus were selected as the control group. Our study reveals increased levels of several phosphatidylethanolamine (PE) lipid species in the serum of ZIKV patients, the majority of them plasmenyl-phosphatidylethanolamine (pPE) (or plasmalogens) linked to polyunsaturated fatty acids. Constituting up to 20% of total phospholipids in humans, plasmalogens linked to polyunsaturated fatty acids are particularly enriched in neural membranes of the brain. The biosynthesis of plasmalogens requires functional peroxisomes, which are important sites for viral replication, including ZIKV. Thus, increased levels of plasmalogens in serum of ZIKV infected subjects suggest a link between ZIKV life cycle and peroxisomes. Our data provide important insights into specific host cellular lipids that are likely associated with ZIKV replication and may serve as platform for antiviral strategy against ZIKV.