Differential role of sphingomyelin in influenza virus, rhinovirus and SARS-CoV-2 infection of Calu-3 cells

Differential role of sphingomyelin in influenza virus, rhinovirus and SARS-CoV-2 infection of Calu-3 cells
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DOI:
10.1099/jgv.0.001593
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发表时间:
2021-01-01
影响因子:
3.8
通讯作者:
To, Kelvin Kai-Wang
To, Kelvin Kai-Wang
中科院分区:
医学3区
文献类型:
--
作者:
Dissanayake, Thrimendra Kaushika;Yan, Bingpeng;To, Kelvin Kai-Wang

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宿主细胞脂质在呼吸道病毒感染的发病机制中起着关键作用。然而,缺乏流感病毒和鼻病毒感染的脂质结构的直接比较。在这项研究中,我们首先比较了支气管上皮细胞系中流感病毒和鼻病毒感染的脂质谱。流感病毒和鼻病毒的大多数脂质特征均下调,尤其是鞘磷脂特征。途径分析表明,鞘脂代谢是最受干扰的途径。功能研究表明,细菌鞘磷脂酶抑制流感病毒和严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)的复制,但促进鼻病毒的复制。这些发现表明,鞘磷脂途径可能是抗病毒治疗的潜在靶点,但应仔细评估,因为它对不同的呼吸道病毒具有相反的作用。此外,鞘磷脂酶对鼻病毒和流感病毒的不同作用可以解释鼻病毒和流感病毒感染之间的干扰。
Host cell lipids play a pivotal role in the pathogenesis of respiratory virus infection. However, a direct comparison of the lipid-domic profile of influenza virus and rhinovirus infections is lacking. In this study, we first compared the lipid profile of influenza virus and rhinovirus infection in a bronchial epithelial cell line. Most lipid features were downregulated for both influenza virus and rhinovirus, especially for the sphingomyelin features. Pathway analysis showed that sphingolipid metabolism was the most perturbed pathway. Functional study showed that bacterial sphingomyelinase suppressed influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, but promoted rhinovirus replication. These findings suggest that sphingomyelin pathway can be a potential target for antiviral therapy, but should be carefully evaluated as it has opposite effects on different respiratory viruses. Furthermore, the differential effect of sphingomyelinase on rhinovirus and influenza virus may explain the interference between rhinovirus and influenza virus infection.