PDF(Pubmed)
Abstract：
T lymphocytes play a primary role in the adaptive antiviral immunity. Both lymphocytosis and lymphopenia were found to be associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While lymphocytosis indicates an active anti-viral response, lymphopenia is a sign of poor prognosis. T-cells, in essence, rarely express ACE2 receptors, making the cause of cell depletion enigmatic. Moreover, emerging strains posed an immunological challenge, potentially alarming for the next pandemic. Herein, we review how possible indirect and direct key mechanisms could contribute to SARS-CoV-2-associated-lymphopenia. The fundamental mechanism is the inflammatory cytokine storm elicited by viral infection, which alters the host cell metabolism into a more acidic state. This \"hyperlactic acidemia\" together with the cytokine storm suppresses T-cell proliferation and triggers intrinsic/extrinsic apoptosis. SARS-CoV-2 infection also results in a shift from steady-state hematopoiesis to stress hematopoiesis. Even with low ACE2 expression, the presence of cholesterol-rich lipid rafts on activated T-cells may enhance viral entry and syncytia formation. Finally, direct viral infection of lymphocytes may indicate the participation of other receptors or auxiliary proteins on T-cells, that can work alone or in concert with other mechanisms. Therefore, we address the role of CD147-a novel route-for SARS-CoV-2 and its new variants. CD147 is not only expressed on T-cells, but it also interacts with other co-partners to orchestrate various biological processes. Given these features, CD147 is an appealing candidate for viral pathogenicity. Understanding the molecular and cellular mechanisms behind SARS-CoV-2-associated-lymphopenia will aid in the discovery of potential therapeutic targets to improve the resilience of our immune system against this rapidly evolving virus.
摘要：
T淋巴细胞在适应性抗病毒免疫中起主要作用。发现淋巴细胞增多和淋巴细胞减少均与严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）有关。虽然淋巴细胞增多表明有积极的抗病毒反应，淋巴细胞减少是预后不良的标志。T细胞,实质上,很少表达ACE2受体，使细胞耗竭的原因变得神秘。此外，新兴菌株提出了免疫学挑战，可能对下一次大流行感到担忧。在这里，我们回顾了可能的间接和直接关键机制如何导致SARS-CoV-2相关淋巴细胞减少.其基本机制是病毒感染引起的炎性细胞因子风暴，这改变了宿主细胞的代谢进入更酸性的状态。这种“高乳酸血症”与细胞因子风暴一起抑制T细胞增殖并触发内在/外在凋亡。SARS-CoV-2感染还导致从稳态造血向应激造血的转变。即使ACE2表达较低，活化T细胞上富含胆固醇的脂筏的存在可能会增强病毒进入和合胞体形成。最后,淋巴细胞的直接病毒感染可能表明其他受体或辅助蛋白对T细胞的参与，可以单独工作或与其他机制协同工作。因此,我们讨论了CD147的作用-SARS-CoV-2及其新变体的新途径。CD147不仅在T细胞上表达，但它也与其他合作伙伴互动，协调各种生物过程。鉴于这些特性,CD147是病毒致病性的有吸引力的候选者。了解SARS-CoV-2相关淋巴细胞减少症背后的分子和细胞机制将有助于发现潜在的治疗靶标，以提高我们的免疫系统对这种快速发展的病毒的抵抗力。
