International Institute of Infection and Immunity, Institutes of Biology and Medical Sciences, Suzhou, China.
Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, China.
EMBO Rep. 2022 Jan 5;23(1):e53466. doi: 10.15252/embr.202153466. Epub 2021 Nov 15.
High-salt diets have recently been implicated in hypertension, cardiovascular disease, and autoimmune disease. However, whether and how dietary salt affects host antiviral response remain elusive. Here, we report that high salt induces an instant reduction in host antiviral immunity, although this effect is compromised during a long-term high-salt diet. Further studies reveal that high salt stimulates the acetylation at Lys663 of p97, which promotes the recruitment of ubiquitinated proteins for proteasome-dependent degradation. p97-mediated degradation of the deubiquitinase USP33 results in a deficiency of Viperin protein expression during viral infection, which substantially attenuates host antiviral ability. Importantly, switching to a low-salt diet during viral infection significantly enhances Viperin expression and improves host antiviral ability. These findings uncover dietary salt-induced regulation of ubiquitinated cellular proteins and host antiviral immunity, and could offer insight into the daily consumption of salt-containing diets during virus epidemics.
高盐饮食最近与高血压、心血管疾病和自身免疫性疾病有关。然而，饮食盐如何影响宿主抗病毒反应仍不清楚。在这里，我们报告高盐诱导宿主抗病毒免疫的即时降低，尽管这种效应在长期高盐饮食时受到损害。进一步的研究表明，高盐刺激 p97 赖氨酸 663 的乙酰化，促进了泛素化蛋白的募集，用于蛋白酶体依赖的降解。p97 介导的去泛素酶 USP33 的降解导致病毒感染时 Viperin 蛋白表达的缺乏，从而显著削弱宿主抗病毒能力。重要的是，在病毒感染期间切换到低盐饮食可显著增强 Viperin 的表达并提高宿主抗病毒能力。这些发现揭示了饮食盐诱导的泛素化细胞蛋白和宿主抗病毒免疫的调节，并为病毒流行期间含盐饮食的日常摄入提供了新的见解。
