Stability of SARS-CoV-2-Encoded Proteins and Their Antibody Levels Correlate with Interleukin 6 in COVID-19 Patients.
Stability of SARS-CoV-2-Encoded Proteins and Their Antibody Levels Correlate with Interleukin 6 in COVID-19 Patients.
复制标题
DOI：
10.1128/msystems.00058-22
复制
发表时间：
2022-06-28
期刊：
影响因子：
6.4
通讯作者：
中科院分区：
文献类型：
--
作者：
2019冠状病毒病（COVID-19）的病原体——严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）的传播已成为一场严重的全球公共卫生危机。因此，了解SARS-CoV-2的分子细节对于对抗病毒的传播和预防未来的大流行至关重要。在这项研究中，我们在全球范围内分析了sars - cov -2编码蛋白的稳定性，研究了它们的降解途径，并确定了它们与患者血浆抗体反应的相关性。我们鉴定出18种半衰期不稳定的蛋白质和6种半衰期较长的相对稳定的蛋白质。不稳定的SARS-CoV-2蛋白主要通过泛素-蛋白酶体途径降解。我们还观察到抗体水平与蛋白质半衰期之间存在显著相关性，这表明稳定的SARS-CoV-2抗原可能更有效地引发抗体反应。此外，研究发现针对NSP10的抗病毒抗体水平与患者全身白细胞介素6 （IL-6）水平呈负相关。这些发现可能会促进新的治疗或诊断方法的发展。SARS-CoV-2是COVID-19的病因，其基因组中携带29个基因。然而，我们对病毒蛋白在生物学和生化方面的认识是有限的。在这项研究中，我们在全球范围内分析了活肺上皮细胞中病毒蛋白的稳定性。重要的是，不稳定的sars - cov -2编码蛋白主要通过泛素-蛋白酶体途径降解。SARS-CoV-2的稳定蛋白，包括刺突和核衣壳，在诱导抗体产生方面更有效。针对NSP10的抗病毒抗体水平与COVID-19患者全身IL-6水平呈负相关。
The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has become a severe global public health crisis. Therefore, understanding the molecular details of SARS-CoV-2 will be critical for fighting the virus’s spread and preventing future pandemics. In this study, we globally profiled the stability of SARS-CoV-2-encoded proteins, studied their degradation pathways, and determined their correlation with the antibody responses in patient plasma. We identified 18 proteins with unstable half-lives and 6 relatively stable proteins with longer half-lives. The labile SARS-CoV-2 proteins were degraded mainly by the ubiquitin-proteasome pathway. We also observed a significant correlation between antibody levels and protein half-lives, which indicated that a stable antigen of SARS-CoV-2 could be more effective for eliciting antibody responses. In addition, levels of antiviral antibodies targeting NSP10 were found to be negatively correlated with systemic levels of interleukin 6 (IL-6) in patients. These findings may facilitate the development of novel therapeutic or diagnostic approaches. IMPORTANCE SARS-CoV-2, the etiological cause of COVID-19, carries 29 genes in its genome. However, our knowledge of the viral proteins in biological and biochemical aspects is limited. In this study, we globally profiled the stability of the viral proteins in living lung epithelial cells. Importantly, the labile SARS-CoV-2-encoded proteins were mainly degraded through the ubiquitin-proteasome pathway. Stable proteins, including spike and nucleocapsid, of SARS-CoV-2 were more effective in eliciting antibody production. The levels of antiviral antibodies targeting NSP10 were negatively correlated with systemic levels of IL-6 in COVID-19 patients.
登录
查看更多内容
影响因子：
16.6
作者：
Kokic G;Hillen HS;Tegunov D;Dienemann C;Seitz F;Schmitzova J;Farnung L;Siewert A;Höbartner C;Cramer P
通讯作者：
Cramer P
影响因子：
168.9
作者：
Huang, Chaolin;Wang, Yeming;Cao, Bin
通讯作者：
Cao, Bin
影响因子：
8.8
作者：
Kitsios, Georgios D.;Yang, Libing;McVerry, Bryan J.
通讯作者：
McVerry, Bryan J.
香烟烟雾提取物通过抑制 PRMT6/AKT 信号传导诱导气道上皮细胞死亡
DOI：
10.18632/aging.202210
发表时间：
2020-12-01
期刊：
Aging
影响因子：
--
作者：
Li T;Fanning KV;Nyunoya T;Chen Y;Zou C
通讯作者：
Zou C
DOI：
10.1038/s41577-021-00553-8
发表时间：
2021-06
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Jones SA;Hunter CA
通讯作者：
Hunter CA