Genetic regulation of short chain fatty acid on Leghorn male hepatoma cells infected with Fowl Adenovirus serotype-4.

Fowl Adenovirus serotype 4 (FAdV-4) infection causes hepatitis-hydropericardium syndrome (HHS), a disease with high mortality in poultry. Short chain fatty acids (SCFAs) are a major gut metabolite that strengthens barrier function, impacts microbiome dynamics, and enhances protective immunity. Among SCFAs, butyrate has been suggested to promote anti-inflammatory effect that reduces tissue damage during viral infections. In this study, we pre-treated Leghorn male hepatoma (LMH) cell line with butyrate, infected them with FAdV-4, and examined genetic regulation related to protective immunity. Differentially expressed genes (DEGs) were identified through RNA sequencing, revealing significant alterations in various cellular pathways during FAdV-4 infection. Butyrate restored the expression of several genes involved in metabolic pathways, including the PPAR pathway. Additionally, butyrate reduced the expression of the anti-viral molecule Oasl and while upregulating il8, which plays a role in immune cell recruitment. These findings suggest that butyrate supports a beneficial antiviral response in host cells during FAdV-4 infection. This study provides the role of SCFAs in modulating host defense mechanisms against avian viral infections.