A gut-derived Streptococcus dysgalactiae protects Micropterus salmoides against MSRV via cell wall-mediated physical trapping of virions.

Gut microbiota play a pivotal role in modulating viral infections in mammals, but their functional contributions and mechanisms in teleost fish remain largely unexplored. Here, we investigated whether intestinal commensals influence Micropterus salmoides rhabdovirus (MSRV) infection in largemouth bass (Micropterus salmoides) and evaluated and characterized the antiviral activity of a candidate commensal isolate. Antibiotic-induced gut microbiota depletion significantly increased host susceptibility to MSRV, without compromising intestinal barrier integrity, indicating that indigenous microbiota confer protection independent of physical barrier function. A gut-derived Streptococcus dysgalactiae strain isolated from healthy bass intestine was administered as a dietary supplement, resulting in successful enrichment, improved survival, reduced viral loads in liver, spleen and intestine, and no detectable intestinal pathology. Mechanistically, we demonstrate that MSRV virions directly bind to bacterial cell wall glucan and peptidoglycan via specific interactions, and this physical sequestration blocks viral attachment and entry into host cells, as evidenced by electron microscopy, ELISA, competitive binding assays, and in vitro infection models. This physical trapping represents a previously unrecognized antiviral strategy that acts upstream of host immunity, complementing the immune system by reducing the initial viral inoculum. Our findings reveal that a gut-derived bacterium can exert direct antiviral activity through virus-bacteria physical interaction, providing a mechanistic basis for the future design of antiviral interventions against rhabdoviral diseases in aquaculture.