A ‘Dynamic Brake’ on RNA Virus Immunity: Researchers Uncover How SESN1 Works

Researchers in China have uncovered how SESN1, a protein that suppresses excessive inflammation during RNA virus infection, works. They describe it as a “dynamic brake” that helps eliminate viruses while preventing an excessive immune response.

A research team led by Pan Mingyu (潘明玉) of Nanjing Medical University published the findings in the Proceedings of the National Academy of Sciences (PNAS) on Aug. 26 (local time).

According to the team, during RNA virus infection, SESN1 acts as a negative regulator of the innate immune response by promoting the degradation of MAVS, a key protein in immune signaling.

With low-dose viral infection, SESN1 levels initially fall and then rise again later. This allows the immune response to remain active early on to eliminate the virus, while preventing excessive cytokine production later.

By contrast, with high-dose viral infection, SESN1 levels remained consistently low, triggering strong cytokine production.

The team also found that SESN1 expression was markedly reduced in patients with severe influenza and was negatively correlated with cytokine levels.

Supplementing SESN1 effectively suppressed cytokine production in human bronchial and tracheal epithelial cells infected with influenza A virus PR8 and in peripheral blood mononuclear cells from patients with severe influenza.

Mechanistically, SESN1 was found to interact with MAVS and then enhance its autophagic degradation through SQSTM1.

The team suggested that SESN1 could be a potential drug target for infectious and inflammatory diseases.