The envelope proteins from SARS-CoV-2 and SARS-CoV potently reduce the infectivity of human immunodeficiency virus type 1 (HIV-1).
The envelope proteins from SARS-CoV-2 and SARS-CoV potently reduce the infectivity of human immunodeficiency virus type 1 (HIV-1).
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DOI：
10.1186/s12977-022-00611-6
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发表时间：
2022-11-19
期刊：
影响因子：
3.3
通讯作者：
中科院分区：
文献类型：
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病毒孔蛋白是参与病毒组装和释放的病毒编码的离子通道。人类免疫缺陷病毒1型（HIV-1）和甲型流感病毒编码病毒孔蛋白。人冠状病毒SARS-CoV-2编码至少两种病毒孔蛋白，一种称为包膜（E）蛋白的75个氨基酸的小跨膜蛋白和一种称为Orf 3a的275个氨基酸的大蛋白。在这里，我们比较了HIV-1在四种不同的β-冠状病毒E蛋白存在下的复制。我们观察到SARS-CoV-2和SARS-CoV E蛋白将传染性HIV-1的释放量减少了约100倍，而MERS-CoV或HCoV-OC 43 E蛋白在较小程度上限制了HIV-1的传染性。从机制上讲，无论是逆转录还是mRNA合成都不参与限制。我们还表明，所有四种E蛋白引起eIF 2-α的磷酸化水平相似，LC 3-I的脂化不能解释限制的差异。然而，转染细胞中的caspase 3活性水平与细胞中的HIV-1限制相关。最后，我们发现，与HIV-1的Vpu蛋白不同，这四种E蛋白并没有显著下调骨髓基质细胞抗原2（BST-2）。本研究的结果表明，虽然来自同源病毒的病毒孔蛋白可以增强病毒释放，但我们表明来自异源病毒的病毒孔蛋白可以抑制HIV-1蛋白的合成和感染性病毒的释放。在线版本包含补充材料，可通过10.1186/s12977-022-00611-6获得。
Viroporins are virally encoded ion channels involved in virus assembly and release. Human immunodeficiency virus type 1 (HIV-1) and influenza A virus encode for viroporins. The human coronavirus SARS-CoV-2 encodes for at least two viroporins, a small 75 amino acid transmembrane protein known as the envelope (E) protein and a larger 275 amino acid protein known as Orf3a. Here, we compared the replication of HIV-1 in the presence of four different β-coronavirus E proteins. We observed that the SARS-CoV-2 and SARS-CoV E proteins reduced the release of infectious HIV-1 yields by approximately 100-fold while MERS-CoV or HCoV-OC43 E proteins restricted HIV-1 infectivity to a lesser extent. Mechanistically, neither reverse transcription nor mRNA synthesis was involved in the restriction. We also show that all four E proteins caused phosphorylation of eIF2-α at similar levels and that lipidation of LC3-I could not account for the differences in restriction. However, the level of caspase 3 activity in transfected cells correlated with HIV-1 restriction in cells. Finally, we show that unlike the Vpu protein of HIV-1, the four E proteins did not significantly down-regulate bone marrow stromal cell antigen 2 (BST-2). The results of this study indicate that while viroporins from homologous viruses can enhance virus release, we show that a viroporin from a heterologous virus can suppress HIV-1 protein synthesis and release of infectious virus. The online version contains supplementary material available at 10.1186/s12977-022-00611-6.
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影响因子：
13.2
作者：
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影响因子：
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影响因子：
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影响因子：
3.3
作者：
Arachchige, Sachith Polpitiya;Henke, Wyatt;Stephens, Edward B.
通讯作者：
Stephens, Edward B.
影响因子：
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通讯作者：
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