Ex vivo analysis of the impact of dsRNA complexed to cationic phytoglycogen nanoparticles on the innate immune response in rainbow trout.

Abstract

As aquaculture intensifies to satisfy the rising global demand for food, viral disease pressure is increasing in farmed fish. The variable efficacy of existing vaccines underscores the need for prophylactic strategies that confer broad antiviral protection. Long double-stranded RNA is a potent inducer of the type I interferon response in rainbow trout that can protect against a broad range of virus families. The current work investigates the effect of a commercially available viral dsRNA mimic, high molecular weight polyinosinic: polycytidylic acid (HMW poly I:C), complexed to a phytoglycogen nanoparticle (Nanodendrix, NDx), on primary gut sac preparations and peripheral blood leukocytes (PBLs). PBLs treated with NDx alone or HMW poly I:C + NDx induced significant increases in metabolism, which is an indicator of phagocyte proliferation and activation. The HMW poly I:C + NDx complex was able to enhance overall phagocytosis in adherent and non-adherent PBL populations while upregulating expression of the antiviral genes mx1 and vig-3 after 24hs while HMW poly I:C alone induced some phagocytosis and mx1 expression at 24h. Using a gut perfusion model, NDx suppressed vig-3 expression in the middle intestine and upregulated its expression in the distal intestine after 2hrs, while HMW poly I:C + NDx upregulated vig-3 expression in the middle intestine after 6hrs and HMW poly I:C alone had no effect. Overall, this preliminary translation of antiviral prophylactic dsRNA therapeutics to an ex vivo study of rainbow trout tissues demonstrates the potential for HMW poly I:C + NDx to be analyzed in vivo for the ability to protect rainbow trout against viral infection.