Hainan Branch of Chinese PLA General Hospital Sanya City, Hainan, China.
PLoS One. 2012;7(7):e41687. doi: 10.1371/journal.pone.0041687. Epub 2012 Jul 26.
Innate immunity to viruses involves receptors such as RIG-I, which senses viral RNA and triggers an IFN-β signaling pathway involving the outer mitochondrial membrane protein MAVS. However, the functional status of MAVS phosphorylation remains elusive.
METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate for the first time that MAVS undergoes extensive tyrosine phosphorylation upon viral infection, indicating that MAVS phosphorylation might play an important role in MAVS function. A tyrosine-scanning mutational analysis revealed that MAVS tyrosine-9 (Y9) is a phosphorylation site that is required for IFN-β signaling. Indeed, MAVS Y9F mutation severely impaired TRAF3/TRAF6 recruitment and displayed decreased tyrosine phosphorylation in response to VSV infection compared to wild type MAVS. Functionally, MAVS Y9 phosphorylation contributed to MAVS antiviral function without interfering with its apoptosis property.
CONCLUSIONS/SIGNIFICANCE: These experiments identify a novel residue of MAVS that is crucially involved in the recruitment of TRAF3/TRAF6 and in downstream propagation of MAVS signaling.
先天免疫系统对病毒的识别依赖于 RIG-I 等受体，该受体能够识别病毒 RNA 并触发包含外线粒体膜蛋白 MAVS 的 IFN-β 信号通路。然而，MAVS 磷酸化的功能状态仍不清楚。
方法/主要发现：本研究首次证明，病毒感染后 MAVS 发生广泛的酪氨酸磷酸化，提示 MAVS 磷酸化可能在 MAVS 功能中发挥重要作用。酪氨酸扫描突变分析显示，MAVS 酪氨酸-9（Y9）是一个磷酸化位点，该位点对于 IFN-β 信号通路是必需的。事实上，与野生型 MAVS 相比，MAVS Y9F 突变严重损害了 TRAF3/TRAF6 的募集，并显示出对 VSV 感染的酪氨酸磷酸化减少。功能上，MAVS Y9 磷酸化有助于 MAVS 的抗病毒功能，而不干扰其凋亡特性。
结论/意义：这些实验确定了 MAVS 的一个新残基，该残基对于 TRAF3/TRAF6 的募集以及 MAVS 信号通路的下游传播至关重要。
