SARS-CoV-2 may affect the immune response via direct inhibition of T cell receptor: Mechanistic hypothesis and rationale.

SARS-CoV-2 may affect the immune response via direct inhibition of T cell receptor: Mechanistic hypothesis and rationale.
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DOI:
10.1016/j.biochi.2021.11.005
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发表时间:
2022-04
期刊:
影响因子:
3.9
通讯作者:
Sigalov AB
Sigalov AB
中科院分区:
生物学3区
文献类型:
--
作者:
Sigalov AB

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在与宿主的共同进化过程中,许多病毒进化出一种膜融合机制,以促进宿主细胞的进入。例如人类免疫缺陷病毒1型(HIV-1)和严重急性呼吸综合征冠状病毒1型和2型(SARS-CoV-1和SARS-CoV-2)。这些病毒也可以感染免疫细胞(如T细胞),这为在这些感染患者中观察到的T细胞淋巴减少提供了一种可能的机制。此前,我们在体内假设并证实,SARS-CoV-1与HIV-1一样,不仅可以利用其融合结构域进入T细胞,还可以直接抑制T细胞受体信号传导。在这里,基于对现有结构和临床数据的分析,我们假设SARS-CoV-2可能使用类似的“解除警报”策略来抑制免疫反应。我们还讨论了这一假设对更好地理解2019冠状病毒病(COVID-19)病理学、开发有效的COVID-19疫苗和改善COVID-19患者临床结果的意义。
During co-evolution with their hosts, many viruses have evolved a membrane fusion mechanism to facilitate host cell entry. Examples are human immunodeficiency virus type 1 (HIV-1) and severe acute respiratory syndrome coronaviruses 1 and 2 (SARS-CoV-1 and SARS-CoV-2). These viruses can also infect immune cells (e.g., T cells), providing one of the possible mechanisms for the T cell lymphopenia observed in patients with these infections. Previously, we hypothesized and confirmed in vivo that like HIV-1, SARS-CoV-1 can use its fusion domain not only to enter the T cell but also to directly inhibit T cell receptor signaling. Here, based on the analysis of available structural and clinical data, we hypothesize that SARS-CoV-2 may use a similar "disarm the alarm" strategy to suppress immune responses. We also discuss the implications of this hypothesis for better understanding coronavirus disease 2019 (COVID-19) pathology, developing effective COVID-19 vaccines and improving clinical outcomes for COVID-19 patients.
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