15 November 2021 – High dietary salt intake induces almost instant reduction in anti-viral immunity, in addition to the already proven associations with hypertension, cardiovascular disease and autoimmune conditions. This has been revealed through research conducted in mice by a predominantly Chinese group, which has also identified the underlying mechanisms involving downregulation of a gene that plays a key role in immunity. However, the study also found that this reduced immunity is quickly reversable, and that switching to a low salt diet might improve host defence against a viral infection while it is taking place. These results were published today in EMBO Reports.
The study identified a signalling protein called viperin that is released by host cells in the presence of viruses as a principal component through which a high salt diet affects viral immunity. Normally, production of viperin is induced by viral infection through action of interferon, a signalling protein released by host cells in response to viral infection. Viperin plays a key role in defence against viruses by inhibiting their replication in various ways, including blocking the release of new virus particles from infected cells.
The researchers found that a short-term high-salt diet promoted viral infection in mice, with further study then revealing it inhibits the expression of anti-viral viperin proteins and in turn substantially reduces cellular antiviral ability. High salt intake does this by degrading another protein called USP33, an enzyme that plays a critical role in stabilizing viperin. That causes levels of viperin in cells to be reduced. This is the first time such action of high dietary salt in degrading cellular proteins has been identified and described, most importantly shedding light on the associated reduction in anti-viral immunity.
However, the study also revealed that the negative impact of a high salt diet on anti-viral immunity waned with time, suggesting that the body can to some extent adjust to it. While a short-term high-salt diet over seven days substantially weakened cellular anti-viral action, when sustained for 30 days levels of viruses and their RNA molecules were then only slightly elevated in the blood and spleens of mice compared with controls fed a diet with normal salt levels. Yet at all stages, conversion to a low salt diet quickly enhanced viperin production and improved host antiviral ability, confirming the reversibility of the process.
The impact of high salt intake on anti-viral immunity is part of a complex immune regulatory process, which works out differently in the case of anti-bacterial defences. On the one hand, high salt intake reduces survival time of Lactobacillus in the intestine, considered a good bacterium that plays a positive role in gut metabolism. Yet, high salt has also been found to enhance defence against bacterial skin infections.
The overall impact of high salt intake is to disrupt immune balance, resulting in unpredictable changes in biological function.
High Salt Activates p97 to Lower Host Antiviral Ability by Restricting Viperin Protein Induction
Yukang Yuan,Ying Miao,Tengfei Ren, Fan Huang, Liping Qian, Xiangjie Chen, Yibo Zuo, Hong-Guang Zhang, Jiuyi He, Caixia Qiao, Qian Du, Qiuyu Wu, Wei Zhang, Chuanwu Zhu, Yang Xu, Depei Wu, Weifeng Shi, Jingting Jiang, Guoqiang Xu and Hui Zheng
Read the full paper: https://www.embopress.org/doi/10.15252/embr.202153466