近日，美国国立卫生研究院Nihal Altan-Bonnet及其团队揭示了先天传感器反应为病毒复制设定了一个超单一的阈值。相关论文于2026年10月29日发表在《细胞》杂志上。

细胞通过触发快速而灵敏的先天免疫反应来抵抗病毒感染，这些反应由细胞质病毒传感器蛋白（CyVSP）——维甲酸诱导基因I（RIG-I）、黑色素瘤分化相关蛋白5（MDA-5）和蛋白激酶R（PKR）——启动。研究人员的单细胞分析揭示，病毒复制需要超单一的病毒基因组输入，显著多于一个，研究人员将其定义为病毒粒子复制输入阈值（VITREP）。该阈值因病毒和细胞类型而异，独立于病毒蛋白合成。通过数学建模和实验测试，研究人员发现超单一的病毒基因组数量会激活CyVSP的负反馈调节因子（NFR），包括死亡相关蛋白激酶1（DAPK1）、Rio激酶3（RIOK3）和蛋白磷酸酶2调节亚基α（PPP2R2A），这些因子抑制先天免疫反应并允许复制。研究人员验证了其模型的关键预测，即下调NFR会减少复制，而上调NFR或共感染细胞则促进复制。总之，这些发现揭示了一种调控病毒感染性和组织嗜性的基本机制。

附：英文原文

Title: Innate sensor responses set a supra-unitary threshold for viral replication

Author: Kojiro Mukai, Dongya Jia, Mamata Panigrahi, Thomas Tayman, Graham Brogden, Ying-Han Chen, Nazmul Haque, Gunjan Arora, Joshua E. Mutterperl, Ian Poe, Chenyu Zhang, Zahin Islam, Ronald Holewinski, Thorkel Andresson, Di Wu, Grzegorz Piszczek, Joseph Marcotrigiano, J. Robert Hogg, Suk See De Ravin, Nasir S. Malik, Avindra Nath, Ekaterina Viktorova, Anna Zimina, George A. Belov, Banu Bayyurt-Kocaba, Grégoire Altan-Bonnet, Nihal Altan-Bonnet

Issue&Volume: 2026-10-29

Abstract: Cells resist viral infection by triggering rapid and sensitive innate immune responses, initiated by cytoplasmic viral sensor proteins (CyVSP), retinoic acid-inducible gene I (RIG-I), melanoma differentiation-associated protein 5 (MDA-5), and protein kinase R (PKR). Our single-cell analysis reveals that viral replication requires a supra-unitary viral genome input, significantly more than one, which we define as the virion input threshold for replication (VITREP). This threshold varies depending on viruses and cell types, independently of viral protein synthesis. Through mathematical modeling and experimental testing, we uncover that supra-unitary viral genome quantities activate negative feedback regulators (NFR) of CyVSP, including death-associated protein kinase 1 (DAPK1), Rio kinase 3 (RIOK3), and protein phosphatase 2 regulatory subunit alpha (PPP2R2A), that suppress innate immune responses and allow replication. We validate key predictions of our model, namely that downregulating NFR reduces replication, whereas upregulating NFR or coinfecting cells promotes replication. Together, these findings reveal a fundamental mechanism governing viral infectivity and tissue tropism.

DOI: 10.1016/j.cell.2026.10.004

Source:https://www.cell.com/cell/abstract/S0092-8674(26)01215-8