Butyrate Reprograms Expression of Specific Interferon-Stimulated Genes

Area of Science:

• Microbiology
• Immunology
• Virology

Background:

• Butyrate, a gut microbiota metabolite, is a known histone deacetylase inhibitor.
• Its impact on viral infections and the type I interferon (IFN) antiviral response remains under-investigated.

Purpose of the Study:

• To investigate the effects of butyrate on viral infections and the antiviral type I interferon (IFN) response.
• To elucidate the mechanisms by which butyrate influences cellular antiviral defense.

Main Methods:

• Assessed butyrate's effect on infection rates of various viruses (influenza, reovirus, HIV-1, etc.).
• Measured levels of IFN-stimulated gene (ISG) products (e.g., RIG-I, IFITM3) and STAT1/STAT2 phosphorylation/translocation.
• Analyzed global gene expression and IFN-induced ISG expression in the presence and absence of butyrate.

Main Results:

• Butyrate increased cellular infection rates across multiple relevant viruses.
• It suppressed key antiviral ISG products (RIG-I, IFITM3) without affecting STAT1/STAT2 signaling.
• Butyrate repressed 60% of IFN-induced ISGs while upregulating 3%, altering IFN responsiveness.

Conclusions:

• Butyrate reprograms the innate antiviral immune response mediated by type I IFNs.
• It creates a proviral cellular environment by dampening the innate immune pathway.
• Findings suggest butyrate could be a tool for increasing virus stocks for research and vaccine generation.