Virion-Associated Cholesterol Regulates the Infection of Human Parainfluenza Virus Type 3
Virion-Associated Cholesterol Regulates the Infection of Human Parainfluenza Virus Type 3
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病毒颗粒相关胆固醇调节 3 型人类副流感病毒的感染
DOI：
10.3390/v11050438
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发表时间：
2019-05
期刊：
影响因子：
4.7
通讯作者：
Qin Yali
中科院分区：
文献类型：
--
作者：
Tang Qiaopeng;Liu Pengfei;Chen Mingzhou;Qin Yali
副粘病毒的基质(M)蛋白与糖蛋白的核衣壳和细胞质尾部结合，从而介导病毒粒子的组装和出芽。我们首先确定了HPIV3融合(F)蛋白的出芽特性，以研究人类副流感病毒3型（HPIV3）的组装机制。我们的研究结果表明，单独表达HPIV3 F蛋白足以启动病毒样颗粒（vlp）的释放，并且F蛋白可以调节M蛋白的vlp形成能力。构建并回收了HPIV3F-Flag，这是一个重组HPIV3，在F蛋白的c端有Flag标记。我们发现，在hpiv3f - flag感染的细胞中，M、F和血凝素-神经氨酸酶（HN）蛋白和病毒基因组可以在脂筏中积累，F蛋白主要以F1的形式存在于VLPs、脂筏和纯化的病毒粒子中。此外，通过甲基β-环糊精（m -β cd）消除胆固醇，评估了胆固醇在病毒包膜和细胞膜中的功能。我们的研究结果表明，由于缺乏胆固醇的内化能力缺陷，HPIV3的传染性明显降低。这些结果表明，HPIV3可能在脂筏中聚集以获取用于HPIV3包膜的胆固醇，这表明破坏HPIV3病毒粒子的胆固醇组成可能是设计抗HPIV3治疗的有用方法。
The matrix (M) proteins of paramyxoviruses bind to the nucleocapsids and cytoplasmic tails of glycoproteins, thus mediating the assembly and budding of virions. We first determined the budding characterization of the HPIV3 Fusion (F) protein to investigate the assembly mechanism of human parainfluenza virus type 3 (HPIV3). Our results show that expression of the HPIV3 F protein alone is sufficient to initiate the release of virus-like particles (VLPs), and the F protein can regulate the VLP-forming ability of the M protein. Furthermore, HPIV3F-Flag, which is a recombinant HPIV3 with a Flag tag at the C-terminus of the F protein, was constructed and recovered. We found that the M, F, and hemagglutinin-neuraminidase (HN) proteins and the viral genome can accumulate in lipid rafts in HPIV3F-Flag-infected cells, and the F protein mainly exists in the form of F1 in VLPs, lipid rafts, and purified virions. Furthermore, the function of cholesterol in the viral envelope and cell membrane was assessed via the elimination of cholesterol by methyl-β-cyclodextrin (MβCD). Our results suggest that the infectivity of HPIV3 was markedly reduced, due to defective internalization ability in the absence of cholesterol. These results reveal that HPIV3 might assemble in the lipid rafts to acquire cholesterol for the envelope of HPIV3, which suggests the that disruption of the cholesterol composition of HPIV3 virions might be a useful method for the design of anti-HPIV3 therapy.
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影响因子：
5.4
作者：
Clemente, Roberto;de Parseval, Aymeric;de la Torre, Juan C.
通讯作者：
de la Torre, Juan C.
影响因子：
3.7
作者：
Fumihiro Sugahara;T. Uchiyama;Hitoshi Watanabe;Y. Shimazu;M. Kuwayama;Y. Fujii;K. Kiyotani;A. Adachi;N. Kohno;Tetsuya Yoshida;T. Sakaguchi
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Fumihiro Sugahara;T. Uchiyama;Hitoshi Watanabe;Y. Shimazu;M. Kuwayama;Y. Fujii;K. Kiyotani;A. Adachi;N. Kohno;Tetsuya Yoshida;T. Sakaguchi
影响因子：
5.4
作者：
Zhang, Guangyuan;Zhang, Shengwei;Chen, Mingzhou
通讯作者：
Chen, Mingzhou
人副流感病毒3型核蛋白的氨基酸对于模板功能和细胞质包涵体形成至关重要
影响因子：
5.4
作者：
Zhang, Shengwei;Chen, Longyun;Chen, Mingzhou
通讯作者：
Chen, Mingzhou
影响因子：
5.4
作者：
Guyader, M;Kiyokawa, E;Trono, D
通讯作者：
Trono, D