SARS-CoV-2刺突蛋白S1激活Cx43半通道并扰乱细胞内Ca2+动力学。

IF 4.3 2区 生物学 Q1 BIOLOGY
Juan Prieto-Villalobos, Claudia M Lucero, Maximiliano Rovegno, Gonzalo I Gómez, Mauricio A Retamal, Juan A Orellana
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引用次数: 0

摘要

背景:严重急性呼吸综合征冠状病毒2(SARS-CoV-2)导致2019年持续的冠状病毒疾病(新冠肺炎)。高度不确定性的一个方面是严重急性呼吸系统综合征冠状病毒2型本身或病毒感染诱导的全身炎症是否直接影响不同组织中的细胞功能和存活。据推测,在新冠肺炎患者中观察到的组织功能障碍和损伤可能依赖于SARS-CoV-2病毒蛋白的直接影响。先前的证据表明,人类免疫缺陷病毒及其包膜蛋白gp120增加了连接蛋白43(Cx43)半通道的活性,对细胞功能和存活产生了负面影响。在这里,我们评估了严重急性呼吸系统综合征冠状病毒2型的刺突蛋白S1是否会影响Cx43半通道的活性。结果:我们发现,通过染料摄取实验测量,刺突S1时间和剂量依赖性地增加了HeLa-Cx43细胞中Cx43半通道的活性。当血管紧张素转换酶2(ACE2)在HeLa-Cx43细胞中表达时,这些反应增强。膜片钳实验表明,尖峰S1增加了具有与Cx43半通道兼容的电导率的单位电流事件。此外,刺突S1引起的Cx43半通道开放触发了ATP的释放,并增加了ATP引起的[Ca2+]i动力学。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
SARS-CoV-2 spike protein S1 activates Cx43 hemichannels and disturbs intracellular Ca2+ dynamics.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the ongoing coronavirus disease 2019 (COVID-19). An aspect of high uncertainty is whether the SARS-CoV-2 per se or the systemic inflammation induced by viral infection directly affects cellular function and survival in different tissues. It has been postulated that tissue dysfunction and damage observed in COVID-19 patients may rely on the direct effects of SARS-CoV-2 viral proteins. Previous evidence indicates that the human immunodeficiency virus and its envelope protein gp120 increase the activity of connexin 43 (Cx43) hemichannels with negative repercussions for cellular function and survival. Here, we evaluated whether the spike protein S1 of SARS-CoV-2 could impact the activity of Cx43 hemichannels.

Results: We found that spike S1 time and dose-dependently increased the activity of Cx43 hemichannels in HeLa-Cx43 cells, as measured by dye uptake experiments. These responses were potentiated when the angiotensin-converting enzyme 2 (ACE2) was expressed in HeLa-Cx43 cells. Patch clamp experiments revealed that spike S1 increased unitary current events with conductances compatible with Cx43 hemichannels. In addition, Cx43 hemichannel opening evoked by spike S1 triggered the release of ATP and increased the [Ca2+]i dynamics elicited by ATP.

Conclusions: We hypothesize that Cx43 hemichannels could represent potential pharmacological targets for developing therapies to counteract SARS-CoV-2 infection and their long-term consequences.

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来源期刊
Biological Research
Biological Research 生物-生物学
CiteScore
10.10
自引率
0.00%
发文量
33
审稿时长
>12 weeks
期刊介绍: Biological Research is an open access, peer-reviewed journal that encompasses diverse fields of experimental biology, such as biochemistry, bioinformatics, biotechnology, cell biology, cancer, chemical biology, developmental biology, evolutionary biology, genetics, genomics, immunology, marine biology, microbiology, molecular biology, neuroscience, plant biology, physiology, stem cell research, structural biology and systems biology.
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