Arginine can help fight tumors and viral infections

To understand how fluctuations in arginine levels caused by diet or disease affect gene expression, Qiu Shuang Wu, an expert at the laboratory, conducted a series of experiments on various disease models, including those of colorectal cancer, influenza, and SARS-CoV-2. In all of these conditions, the researchers observed abnormally low levels of arginine. In cell cultures, Wu examined which proteins became less abundant when the amino acid was scarce.

It turned out that arginine deficiency reduces the level of 414 proteins, most of which are associated with the known molecular functions of arginine. The most unexpected was that the lack of amino acid suppressed the expression of three HLA genes encoding MHC‑I proteins. These proteins are located on the surface of cells and show T‑lymphocytes foreign fragments, so the immune defense against viruses and cancer cells is launched.

The mechanism of the disorder turned out to be related to the peculiarities of the genetic code: the MHC‑I protein contains many arginine-coded regions, and this amino acid is encoded by six different codons (triplets of nucleotides) at once. In the conditions of a shortage of arginine, the ribosomes that assemble proteins stopped when trying to synthesize MHC‑I, as they simply did not have enough of the right amino acid. Because of this, significantly fewer proteins were produced that could signal to T‑cells about the presence of cancer or viral proteins, and pathogens were given the opportunity to remain undetected.

Experiments on mice confirmed the importance of arginine levels for health. Animals on a diet with a low content of arginine were more likely to develop colon tumors, while those on a diet with a high content of the amino acid were less likely to do so. In experiments with models of influenza and SARS‑CoV‑2, a similar pattern was observed. Mice that received more arginine in their diet were able to tolerate viral infections more easily. Moreover, it was found that even adding arginine after the influenza infection improved the condition of the animals, which was a surprise to the researchers. They knew about the effect of arginine on gene expression from genetic models, but they didn’t expect dietary manipulations to be so effective.

According to the authors, the consumption of a specific amino acid can directly regulate gene expression by selectively adjusting translation (the process of protein assembly). This mechanism likely applies not only to arginine and MHC-I, but also to many other proteins and amino acids.

The findings are particularly significant in the context of aging and nutrition. As we age, arginine levels naturally decrease, which can create favorable conditions for the development of colorectal cancer and increase vulnerability to respiratory viruses. According to Soheil Tavazoee, the combination of poor nutrition and age-related arginine decline can create an environment conducive to the onset of cancerous processes.

Researchers believe that arginine supplements can be tested relatively quickly in patients undergoing immunotherapy or used for prevention in high-risk groups exposed to viral pathogens. Given that arginine is inexpensive and widely available, clinical trials in this area may begin in the near future. The team is also currently exploring whether changes in the consumption of other amino acids can have a positive impact on various diseases.