The Function behind the Relation between Lipid Metabolism and Vimentin on H9N2 Subtype AIV Replication.

The Function behind the Relation between Lipid Metabolism and Vimentin on H9N2 Subtype AIV Replication.
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DOI:
10.3390/v14081814
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发表时间:
2022-08-18
期刊:
Viruses
影响因子:
--
通讯作者:
--
中科院分区:
其他
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由H9N2亚型禽流感病毒(AIV)引起的禽流感对养禽业的健康发展构成极大威胁。波形蛋白与细胞内脂代谢密切相关,在病毒感染过程中起着重要作用。然而,脂代谢和波形蛋白在H9N2AIV复制中的作用尚不清楚。本文研究了AIV感染前后波形蛋白基因敲除(KO)细胞和人宫颈癌细胞(HeLa)胆固醇水平和3-羟基-3-甲基戊二酰辅酶A还原酶(HMGCR)磷酸化水平的变化。结果表明,与未感染H9N2亚型AIV的对照组相比,病毒感染后KO和HeLa细胞的胆固醇含量显著增加,HMGCR磷酸化水平降低。此外,在用胆固醇抑制剂洛伐他汀处理的细胞中,病毒复制受到显著抑制。与对照组相比,感染病毒组KO和HeLa细胞中调节HMGCR酶活性的腺苷酸活化蛋白激酶(AMPK)均受到抑制,且KO HeLa细胞中AMPK的磷酸化水平明显低于HeLa细胞。此外,MβCD处理后,HeLa细胞中病毒血凝素(HA)基因水平显著降低,而KO HeLa细胞中HA基因水平显著升高。此外,在病毒感染的MβCd处理的HeLa细胞中,波形蛋白的表达显著增加,并在外源性胆固醇回填MβCd处理的细胞后恢复到正常水平。因此,在病毒入侵细胞的结合阶段破坏脂筏可显著减少病毒感染。这些研究表明,脂筏和胆固醇水平可能是H9N2亚型禽流感病毒感染人源细胞的关键因素,波形蛋白可能在调节脂质对病毒复制的作用中发挥重要作用,从而提供了一个重要的抗流感病毒靶点。
Avian influenza caused by H9N2 subtype avian influenza virus (AIV) poses a great threat to the healthy development of the poultry industry. Vimentin is closely related to intracellular lipid metabolism, which plays an important role during the viral infection process. However, the function of lipid metabolism and vimentin on H9N2 AIV replication is unclear. In this paper, the cholesterol level and 3-hydroxy-3-methylglutaryl coenzyme a reductase (HMGCR) phosphorylation were investigated in vimentin knockout (KO) and human cervical carcinoma cells (HeLa) cell with or without AIV infection. The results showed that compared to the control group without infected with H9N2 subtype AIV, the cholesterol contents were significantly increased, while HMGCR phosphorylation level was reduced in both KO and HeLa cell after virus infection. Furthermore, viral replication was significantly inhibited in the cells treated with the cholesterol inhibitor lovastatin. Compared with the control group, adenylate activated protein kinase (AMPK), a kinase regulating HMGCR enzymatic activity was inhibited in both KO and HeLa cells in the infected virus group, and AMPK phosphorylation levels were significantly lower in KO HeLa cell than that of HeLa cells. Additionally, after MβCD treatment, viral hemagglutinin (HA) gene level was significantly decreased in HeLa cells, while it was significantly increased in KO HeLa cells. In addition, vimentin expression was significantly increased in MβCD-treated HeLa cells with the viral infection and returned to normal levels after exogenous cholesterol to backfill the MβCD-treated cells. Therefore, the disruption of lipid rafts during the binding phase of viral invasion of cells significantly reduced viral infection. These studies indicated that the lipid rafts and cholesterol levels might be critical for H9N2 subtype AIV infection of human-derived cells and that vimentin might play an important role in the regulation of lipids on viral replication, which provided an important antiviral target against influenza virus.
DOI: 10.1371/journal.pone.0080304
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期刊: PloS one
影响因子: 3.7
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DOI: 10.3390/v14061172
发表时间: 2022-05-28
期刊: Viruses
影响因子: --
作者:
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发表时间: 2013-02-01
期刊: AUTOPHAGY
影响因子: 13.3
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发表时间: 2004-02-06
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